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Fabio Sterpone. MOLECULAR MODELLING AND SIMULATION: FROM BIOLOGICAL SYS-TEMS TO MATERIALS . Theoretical and/or physical chemistry. Université Denis Diderot 2012. �tel-01541650�
UNIVERSITE PARIS VII – DENIS DIDEROT
U.F.R. Chimie
MEMOIRE
Présenté pour obtenir
L’habilitation de Diriger des Recherches
Université Denis Diderot (Paris 7)
par
Fabio STERPONE
“MOLECULAR MODELLING AND SIMULATION:
FROM BIOLOGICAL SYSTEMS TO MATERIALS”
Soutenance 25 Mai 2012
Jury
Madame Catherine Etchebest rapporteur DSIMB, Inserm, Paris Monsieur Thomas Simonson rapporteur Ecole Polytechnique, Paris Monsieur Mounir Tarek rapporteur Univ de Lorraine, Nancy
Monsieur Daniel Borgis examinateur Ecole Normale Supérieure, Paris Monsieur Manuel F. Ruiz-Lopez examinateur Univ de Lorraine, Nancy
Summary
I presently work at the Laboratoire de Biochimie Théorique in the Institut de Biologie et Physico-Chimique (CNRS). I have been hired as researcher (CR1) at CNRS in 2010. Previously I have been post-doc for about seven years spent in different research environments.
I am a scientist with a strong background in computational biophysics and physical chemistry. My research activity involves the application and development of computational methods for tackling problems such as protein thermostability and hydration, membrane fusion and surfactant aggregation, optical and electronic properties of semiconducting polymers.
The study of thermophilic protein is my principal axes of research for the next years. This research will benefit of all the expertise acquired during my past training. For example I want to unveil how the behavior of interfacial water may impact the thermodynamics stability of a protein. My past study on the structure and dynamics of water at the interface with proteins and micelles is a solid background for this future challenge. Moreover, in order to investigate the function of a protein in the high temperature regime a detailed quantum treatment of some degrees of freedom is necessary. My past activity in the field of quantum/classical as well as ab initio simulation will support this part of the research. The research on thermophilic proteins is funded by the European Research Council (ERC) via the starting grant IDEAS. A post-doc and a PhD student have joined me on this research topic. Extra-mural collaborations have been already established; I mention the collaboration with D. Madern at the Institut de Biologie Structurale (Grenoble, France), M. Maccarini at the ILL (Grenoble, France), S. Melchionna at CNR (Rome, Italy)
My second line of research concerns the study of membrane fusion and in particular the role of the protein SNARE. My study will be based on a multi-scale approach using both atomistic and coarse-grain models. This research will benefit from my expertise in the field of soft-matter. My investigation will be supported by intense intra-mural collaborations, namely with P. Derreumaux and M. Baaden.
Along the years I had an intense activity in code development. I am author of a code for the quantum/classical simulation of π-conjugated polymers in both ground and excited state. This code is currently used in collaboration with the group of P.J. Rossky at the university of Texas at Austin and I. Burghardt at Frankfurt University for investigating the optical and electronic properties of semiconducting plastic materials. I have also given a contribution to the development of the engine for the ab initio simulation CP2K. I have specifically implemented a sophisticated method for advanced sampling, the Temperature Accelerate Molecular Dynamics, for studying hydrogen storage and release in materials.
KEYWORDS: Computer simulation, protein hydration and stability, membrane fusion, classical, quantum/classical and ab initio molecular dynamics.
Table of Contents
Introduction __________________________________________________________ 4
Curriculum Vitae ______________________________________________________ 6
Student Advising______________________________________________________ 10
Research activity______________________________________________________ 12
Biological water ...13 Micelles ...22 Energy storage & conversion...29Future Projects _______________________________________________________ 38
Thermos...39 Snares...42CONCLUSION _______________________________________________________ 44
Bibliography _________________________________________________________ 45
Annexes _____________________________________________________________ 47
A.1 Abstracts...47 A.2 Software development...55Introduction
In this memoire I present a summary of my research activity and an overview of my future projects. In the first chapter I present a detailed Curriculum Vitae reporting on my education, my technical experience, my teaching activity as well as my role in the organization of scientific meetings. The second chapter is dedicated to my activity of supervision of students and post-docs. The presentation of my past research (chapter 3) is divided in three main paragraphs, each focusing on a different axis of research. A short presentation of my on going projects concludes the memoire. In order to facilitate the reading of my resume I have included in the annex the abstracts of my publications.
Here below I briefly introduce the body of my memoire. Let’s start with a first consideration: I have been post-docs for about seven years before being hired as CR1 researcher at CNRS and join the Laboratoire de Biochimie Théorique at IBPC. During this long period I had the opportunity to challenge my self in different fields of research and to acquire a deep expertise in computer simulations as well as to be exposed to various scientific environments.
My broad expertise spans the field of classical molecular simulation of biomolecules to the application of quantum methods to material science. Since my PhD my work in the field of computer modeling was always accompanied by intense software development. For example during my post-doc at the university of Texas I have developed a code for the quantum/classical simulation of ground and excited state dynamics of π-conjugated polymers. This code is currently used in the group of Prof. P.J. Rossky for the research in the field of organic electronics. Later, during my work at the High Performance Computing center Caspur (Italy) I had the opportunity to refine my skills in programming by working in the field of Quantum Monte Carlo and ab initio MD. The experience at HPC Caspur was key also for acquiring expertise in the field of parallel computing.
The drawback of being a “scientific rover” was the difficulty to settle down and accomplish those “standard” activities that complement the research effort, i.e. monitoring students and teaching. I am catching up the lost time. For example in recent years and thanks to the on going collaboration with D. Laage at Ecole Normale Supérieure (ENS) in Paris, I have been regularly involved in teaching activity. In particular I am in charge of the tutoring associated to the course “Chemical Reactivity” (Dept. de Chimie, ENS).
During my short term stay in Italy and since my return in France as post-doc at ENS I have been also involved in supervising master and PhD students as well as post-docs. Most of this activity concerned the study of hydrated interfaces, a field in which I am very active.
Presently, thanks to financial support of the European Research Council (starting grant IDEAS, project Thermos) I had the opportunity to create my own group of research. Nowadays a post-doc and a PhD student joined me in the challenging project on thermophilic proteins.
I want to conclude this short introduction spending a few words on those extra-academic activities that helped me in acquiring a broad perspective for my research: when I was student I have organized meetings for students for diffusing and discussing cutting-edge scientific research, later I have participated to innovative editorial activities focused on social and political impacts of research (i.e. webzine, radio pod-casting) and later as researcher I have worked as editor for the Italian Scientific Encyclopedia Treccani caring of the volumes for physics and chemistry of the renewed edition.
Curriculum Vitae
Fabio Sterpone, PhD
Laboratoire de Biochimie Théorique, Institut de Biologie Physico-Chimique, 13 Rue Pierre et Marie Curie, 75005 Paris, France
[email protected] , Phone : +33-1-58415177. Fax: +33-1-58415020
SUMMARY
I am a scientist with a strong background in computational biophysics and physical chemistry. My research activity involves the application and development of computational methods for tackling problems such as protein thermostability and hydration, membrane fusion and surfactant aggregation, optical and electronic properties of semiconducting polymers.
RESEARCH EXPERIENCES
2010- CNRS, Institut de Biologie et Physico-Chimique. Paris, France CR1 researcher
2009-2010 Ecole Normale Supérieure Paris, France Talent Post-Doc Program. Advisor: Prof. J.T.Hynes and Dr D.Laage
• Research: « Mapping of protein hydration using classical simulations »
2006-2008 Caspur, High Performance Computing Center Rome, Italy Researcher. Advisor: Dr S.Meloni and Prof. L. Guidoni
• « Simulations of Quantum Monte Carlo: interface between QMC and DFT methods»
2004-2006 University of Texas at Austin Texas, US Post-Doc. Advisor: Prof. P.J. Rossky
• « Quantum-classical simulations of conjugated polymers »
2001-2004 University « Pierre et Marie Curie » / CEA Paris, France PhD research in biophysics. Advisor: Prof. D. Borgis and Dr. M. Marchi
• « Computer Simulations of the electron transfer in Photosynthetic Proteins »
1999-2000 Commissariat Energie Atomique (CEA) Saclay, France
Research Training. Advisor: Dr. M. Marchi
• « Computer Simulations of the Hydration Dynamics of proteins »
EDUCATION
2001-2004 University “Pierre et Marie Curie” Paris, France PhD in Biophysics (Ecole Doctorale Inter///Bio)
Advisor : Prof. D. Borgis and Dr. M. Marchi
1992-1999 University of Rome “La Sapienza” Rome, Italy B.Sc in Physics. Final Score 110/110 cum laudem
TECHNICAL SKILLS
• Programming Languages: Fortran 77/90, shell scripting, Library MPI and OpenMP for parallel computation, HTML, ActionScript for Flash, ASP.
• Software Development: PPV-Code (Quantum/Classical Simulations of organic polymers, in use at the University of Texas, PJ Rossky’s group, 15,000 line of fortran code); CP2K (contribution to development, http://cp2k.berlios.de/), Library for Input Data (in use at HPC center Caspur, Rome Italy).
• Operating Systems: Unix/Linux, Mac OSX, Window.
• Simulation Techniques: Classical Molecular Dynamics, Non-adiabatic quanto/classical Molecular Dynamics, ab initio Molecular Dynamics, Quantum Monte Carlo, free energy calculations, polarizable force fields.
• Software for molecular simulations: Namd, Orac, DL-POLY (Classical MD); CP2K (ab initio simulations); QCFF, MOLARIS, Gamess (Quantum Chemistry), TurboPair (Quantum Monte Carlo)
• Graphic Software: Rasmol, MolMol, InsightII, VMD, Pymol, Gheochem, Molscript, Raster3D, Pov-Ray, AcdLabs, MatLab, Xmgrace, GnuPlot.
TEACHING EXPERIENCES
• 2011. Lecturer in “Chemical Reactivity”, ENS, Paris, France. (10 hours) • 2010. Lecturer in “Chemical Reactivity”, ENS, Paris, France. (10 hours) • 2008. Advisor for B.Sc in Physics, University of Rome “La Sapienza”, Italy.
• 2007. Lecturer in “Advanced School of Quantum Monte Carlo”, Sissa, Trieste, Italy. (5 hours) • 2007. Advisor in the Master program EU “Erasmus Mundus AtoSIM”.
• 2006. Lecturer in “Atomistic Simulations”, University of Rome “La Sapienza”, Italy. (10 hours)
ACADEMIC ACHIEVEMENTS
• 2011. “Thermos”, ERC-Starting Grant (1,225,000 Euro, over 5 years and including personal salary) • 2009. “Fondation P-G de Gennes”, Grant for talent POST-DOC, Paris, France (60,000 Euro for salary)
• 2006. Qualification for researching at Ente Nazionale per l’Energia e l’Ambiente, Italy. Section: Computer Modeling. • 2005/2009. Qualification for teaching and researching at the French University (“Maître de conferences”).Sec.28/30/31/64 • 2001-2004. Fellowship from Commissariat Énergie Atomique and Égide, Paris, France.
• 2001/2003. Fellowship from Fondazione « Angelo della Riccia », Florence, Italy.
REVIEWER ACTIVITY
Reviewer for the American Chemical Society (J. Phys. Chem., Langmuir), the American Institute of Physics (J. Chem. Phys.) and the Institute of Physics (Phys. Biol.)
SELECTED CONFERENCES AND WORKSHOPS
• Local Organizer of the conference « Ab initio modelling of biomolecules: towards computational spectroscopy », (2007), University of Rome “La Sapienza”, Italy.
• Organizer of workshops for students: «Science of complexity», «Biotechnology», «The Human Genome Project», (1996/1997) University of Rome “La Sapienza” (Italy).
• June 2009. Oral Contribution: « H-Bond dynamics near amino acids », Journée de Modélisation, Paris, France.
• November 2008. Oral Contribution: « Dissecting H-Bond in water from Quantum Monte Carlo calculations », Quantum Monte Carlo Methods, Trento, Italy.
• July 2005. Gordon Conference « Liquid, Chemistry and Physics of », NH, US. Poster section: « Exploring micelle dehydration : the H-bond networks ».
• June 2004. Gordon Conference « Photosynthesis », Roger William University, Bristol, RI, US. Poster Section: « Electron transfer in Reaction Center of Rb.sphaeroides ».
• September 2002. « 4th European Conference on Computational Chemistry », Assisi, Italy. Poster Section: « Dynamical properties of biological water ». Award: Best Poster.
• January 2003. Tutorial: « The MPI library for parallel computation », C.E.A. Saclay, France.
• June 2001. Workshop « Electrostatic for Complex Molecular Systems: Continuum Model and Beyond », Lyon, France. • September 2000. Tutorial: « Car-Parrinello Molecular Dynamics », Cecam, Lyon, France.
High Performance Computing: Allocated Grant
2011 Grant STD11-426,STD11-446,STD11-907, gpu11-907. HPC Caspur.
2009 Grant STD09-366. The grant supported the following publications: 17,20,21 (see publications list below). An extra
publication fully based on simulations carried out at Casur HPC is now in preparation.
EXTRA-ACADEMIC ACTIVITIES
• Editor and consultant for the publishing house Treccani, « The new encyclopedia of science and technology », (2006-2008).
• Author of the books « Il sapere liberato » (« The freed knowledge »), Feltrinelli, 2005, Milan (Italy) and « Scienza S.P.A. », DeriveApprodi, 2002 Rome (Italy)
• Author and speaker for podcasting Radio « RadioLaser ». Amisnet. www.amisnet.org (2004-2007).
• Webmaster and contributions to an electronic magazine for scientific divulgation (e-laser.org) (2002-2006). PUBLICATIONS
(h index = 10, Total Citations = 451 )
1) F.Sterpone, G.Briganti, C.Pierleoni, « Molecular Dynamics study of spherical aggregates of chain molecules at different
degree of hydrophilicity in water solution », Langmuir 2001, 17, 5103-5110.
2) F.Sterpone, M.Ceccarelli, M.Marchi, « Dynamics of hydration in Hen Egg White Lysozyme », J.Mol.Biol., 2001, 311,
429-439.
3) M.Marchi, F.Sterpone, M.Ceccarelli, « Water rotational relaxation and diffusion in hydrated Lysozyme », J. Am. Chem. Soc. 2002, 124, 23, 6787-6791.
4) F.Sterpone, M.Ceccarelli, M.Marchi, « Linear response and electron transfer in complex biomolecules systems and
Reaction Center Protein », J. Phys. Chem. B 2003, 107, 11208-11215.
5) F.Sterpone, C.Pierleoni, G.Briganti, M.Marchi, « Temperature dehydration of C12E6 micelle », Langmuir 2004, 20,
4311-4314.
6) S.Abel, F.Sterpone, S. Bandyopadhyay, M.Marchi, « Molecular modeling and simulation of AOT-water reverse Micelles
in iso-octane: structural and dynamic properties », J. Phys. Chem. B. 2005, 108, 19458-19466.
7) G.Briganti, G.D’Arrigo, M.Maccarini, C.Pierleoni, F. Sterpone, « Hydration and thermodynamic equilibrium of nonionic
surfactant solution », Colloids and Surfaces 2005, 261, 93-99.
8) F. Sterpone, G. Marchetti, C. Pierleoni, M. Marchi, « Molecular modeling and simulation of water near model micelles :
Diffusion, rotational relaxation and structure at the hydration interface ». J. Phys. Chem. B. 2006, 110, 11504-11510
9) F. Sterpone, C. Pierleoni, G. Briganti, M. Marchi, « Structure and dynamics of hydrogen bonds in the interface of a
C12E6 spherical micelle in water solution: A MD study at various temperatures ». J. Phys. Chem. B. 2006, 110, 18254-18261
10) F. Pizzitutti, M. Marchi, F. Sterpone, P.J. Rossky, « How Protein Surfaces Induce Anomalous Dynamics of Hydration
Water ». J. Phys. Chem. B. 2007, 111, 7584-7590.
11) F. Sterpone, P.J. Rossky, « Molecular modeling and simulation of conjugated polymer oligomers: Ground and excited
state chain dynamics of PPV in the gas phase ». J. Phys. Chem. B 2008, 112, 4983-4993
12) F. Sterpone, G. Briganti, S. Melchionna, C. Pierleoni « Pressure induced core packing and interfacial dehydration in
nonionic C12E6 micelle in acqueous solution ». Langmuir, 2008, 24, 6067-6071.
13) F. Sterpone, L. Spanu, L. Ferraro, S. Sorella, L. Guidoni « Water-water hydrogen bond studied by QMC ». J. Chem.Theory and Comput. 2008, 4, 1428-1432.
14) F. Sterpone, C. Bertonati, G. Briganti, S. Melchionna « Key role of proximal water on protein thermostability ». J.Phys.Chem.B., 2009, 113, 131-137.
15) F. Sterpone, M. Bedard-Hearn, P.J. Rossky, « Non adiabatic mixed quantum-classical simulation of p-stacked PPV
oligomers in the groud state and excited states ». J.Phys.Chem. A, 2009, 113, 3427–3430
16) F. Sterpone, G. Briganti and C. Pierleoni, « Sphere vs Cylinder: The effect of packing on the structure on non ionic
hydrophilic hydrogen-bond acceptor groups », J. Phys. Chem. B, 2010, 114, 2083-2089
18) F. Sterpone, C. Bertonati, G. Briganti, S. Melchionna, “Water around thermophilic proteins: the role of charged and polar
atoms », J. of Physics: Condensed Matter, 2010, 22, 28413
19) M. Bedard-Hearn, F. Sterpone, P.J. Rossky, « Non adiabatic simulations of exciton dissociation in
poly-p-phenylenevinylene oligomers ». J.Phys.Chem. A, 2010, 114, 7661–7670
20) D. Laage , G.Stirnemann, F.Sterpone, R. Rey, J.T. Hynes, «Reorientation and allied dynamics in water and aqueous
solution », Ann. Rev. Phys. Chem., 2011, 62, 395-416.
21) G. Stirnemann, F. Sterpone, D. Laage, « Dynamics of water in concentrated solutions of amphiphiles: key roles of local
structure and aggregation » J. Phys. Chem . B, 2011, 115, 3254-3262.
22) F.Sterpone, S.Melchionna, « Role of packing, hydration and fluctuation on Thermostability”, Chapter for “Thermostable
proteins: Structural stability and design ». CRC Press- Taylor and Francis. L. Nilsson and S.Sen Eds.
23) F. Sterpone, R. Martinazzo, A.N. Panda, I. Burghardt, « Coherent Excitation Transfer Driven by Torsional Dynamics:
a Model Hamiltonian for PPV Type Systems », Zeitschrift für Physikalische Chemie, 2011, 255, 541-551.
24) D. Laage, G. Stirnemann, F. Sterpone, J.T. Hynes, « Water Jump Reorientation : From Theoretical Prediction to
Experimental Observation », Acc. Chem. Res., 2012, 45, 53-62.
25) F. Sterpone and S. Melchionna, «Thermophilic proteins : insight and perspective from in silico experiments », Chem.Soc.Rev. 2012, 41, 1665-1676.
26) F. Sterpone, G. Stirnemann, D. Laage, « Magnitude and molecular origin of water slowdown next to protein », 2012, 134, 4116-4119.
27) F. Sterpone, S. Bonella, S. Meloni, “Exploring dehydrogenation process in Alanates via Temperature Accelerated ab
Student Advising
S. Abel. PhD University of Paris VI UPMC (2007)
PhD Thesis: “Micelles inverses d’AOT et de C12E4, structure et évaluation de leur compressibilité par simulation
de dynamique moléculaire”
DSV, CEA, Saclay, France
Advisor (M. Marchi, CEA, Saclay, France)
In his Thesis S. Abel studied using molecular dynamics simulations the structural properties of ionic (AOT) and non-ionic (C12E4) reverse micelles (RM) in apolar solvent. In particularly, he has examined 1) the structural and volumetric properties of the micelles as a function of their sizes and 2) the influence of the micelle water core size on the structural changes of a confined peptide (an alanine peptide).
S. Abel is now researcher at the C.E.A. Our work was published in J. Phys. Chem. B, see Ref. 6 in the publication list.
Carlos Vegas. “Erasmus Mundus AtoSIM” Master Program. (January 2007- June 2007)
Master Thesis: “Modeling the blockage of Kcsa Potassium channel by MD simulations” Physics Department University of Rome “La Sapienza”, Italy
Co-Advisor (Prof. L. Guidoni, University of L’Aquila, Italy)
The effect of fluorination of some aromatic residues located at the gate of the Shaker potassium channel on the blockage activity of tetraethilammonium (TEA+) was studied via MD simulations. Firstly, the Force Field (FF) for
the fluorinated amino acid (Phenylalanine) with a different degree of fluorination has been developed to match coherently the Amber FF. Then, preliminary simulations have been carried out in order to investigate the interaction with the TEA+.
M. Montagna. Bachelor in Science. (June 2008-December 2009)
B.Sc. Thesis: “Spectroscopic properties of water at the interface with small hydrophobic solutes” Physics Department University of Rome “La Sapienza”, Italy
Co-Advisor (Prof. L. Guidoni, University of L’Aquila, Italy)
The vibrational properties of water at the interface with hydrophobic solutes have been investigated using ab initio MD simulation based on the Car-Parrinello technique. This work is aimed to understand if a spectroscopic signature of the hydrophobic effect can be extracted via computer simulation. The results indicated that the hydration shell of an hydrophobic particle is flexible and it is not a rigid cage, moreover at low frequency (~200 cm-1) a difference between interfacial water and bulk water is only visible when an explicit treatment of the electronic degree of freedom is included.
G. Stirnemann. PhD University of Paris VI (June 2009-October 2010)
PhD Thesis: “Water and hydrogen bond dynamics in solution: from bulk to biomolecular environment” Chemistry Department, Ecole Normale Supérieure, Paris, France
Advisor (D. Laage, ENS, Paris, France)
During his thesis, G. Stirnemann has accomplished a huge work studying the reorientational dynamics of water in different contexts. My advising and collaboration concerned specifically the problem of water dynamics at the interface of biological systems such as isolated amino acids and protein and in aqueous amphiphilic solution. Moreover my experience in the study of volumetric properties of liquid was shared for studying the heterogeneous dynamics of pure water at low temperature. As a result of this advising/collaboration several papers have been published, see Ref. 17, 20, 21 in the publication list. Other works are under preparation.
P. Marquetand, Post-Doc (October 2009-October 2010)
Department of Chemistry, Ecole Normale Superieure, Paris, France Supervisor (Prof. J.T. Hynes, ENS, Paris, France)
P.Marquetand studied the dynamics of water in the minor and major grooves of DNA. The extended jump model is applied to study how the topological confinement and the energetic of the solute/solvent hydrogen bond network influence the reorientation of water at the DNA surface. The goal of the study is to understand how the
structure/dynamics of interfacial water may contribute to the binding process to DNA.
P. Marquetand is now researcher in the institute of physical chemistry at the University of Iena. Our work is almost concluded and a publication is under preparation.
O. Rahaman, Post-Doc (July 2011-)
Laboratoire de Biochimie Théorique, IBPC, Paris, France Advisor (F.Sterpone, IBPC, France)
Dr. Rahama joined my group in July 2011. His post-doc is funded by the ERC standard grant Thermos. His project focuses on the study of hydration water of thermophilic proteins. We ere interested in understanding weather or not interfacial water strucutre and/or dynamics may contribute to protein stability.
M.Kalimeri, PhD (October 2011-)
Laboratoire de Biochimie Théorique, IBPC, Paris, France
Advisor (F.Sterpone, IBPC, France and P. Derreumaux IBPC, France)
M. Kalimeri joined as PhD my group in October 2011. The PhD is funded by the ERC standard grant Thermos. Maria is tackling the problem of protein thermostability by focusing on the rigidity of the protein matrix. Common believe states that thermophilic proteins are more rigid than their mesophiolic homologues. However recent experiments and theoretical studies are challenging this idea. We will use computational method to inquire this open problem.
Research activity
A look to the past
Concluding my studies in physics I was firmly convinced to pursue my academic research as an experimentalist in the field of soft matter. Unfortunately at the due time I did not found any available subject in this field for my thesis of Laurea*. Instead it was proposed to me to accomplish a theoretical/computational study of self-aggregating systems under the supervision of Prof. C. Pierleoni. I accepted and I here I am.
Later, I joined the laboratory of M. Marchi at the C.E.A. for my PhD. I was suddenly moving into the field of biomolecular simulations.
During my post-doc at the University of Texas in the group of Prof. P.J.Rossky I did another switch. I opened a second line of research learning/developing/applying quantum-classical computational methods to material science.
After a short stay in Italy where I worked in the High Performance Computing center Caspur, I returned to France thanks to the opportunity offered to me by D. Laage at ENS, Paris. I worked with him on the theoretical aspects of protein hydration. The Fondation P-G de Gennes supported my research via the talent post-doc program.
I would describe the research I conducted so far as a sampling process: I sampled different systems and different computational techniques. A mixture of curiosity and “orror-vacui” probably motivated my non-linear scientific evolution.
In the following I will present a short discussion on the main topics of my past research activity: the hydration of biomolecules, the properties of micellar systems, the study of materials for energy storage and conversion.
1
Biological water
The majority of proteins lives and functions in the aqueous environment of the cytoplasm. Water is then considered key for their stability and dynamics, and ultimately for their activity [1]. Actually, water forms a hydration skin around the protein surface that is intimately coupled to the protein motion; at the same time water can penetrate into internal cavities, superficial clefts and active sites thus playing a role in protein stability and function.
In this paragraph I will overview my works on the hydration of biomolecules. This research has been accomplished during different stages of my career, starting with my PhD and continued independently along my several post-docs. Excited by new experimental findings, motivated by unsolved theoretical questions and supported by stimulating new collaborators I always reserved a portion of my time to this intriguing problem. Indeed I consider that a full understanding of the role of hydration on protein stability and function is key for new challenges as the design of stable proteins, the search for efficient protein inhibitors, the engineering of bio-functionalized nano-materials. Thanks to the acquired expertise in the field I had the opportunity in the recent years to supervise the research activity of several students and a post-doc.
Internal waters
Thanks to the increased number of protein crystallographic structures available in public databases it is now possible to investigate systematically the role of water molecules that are found embedded in the protein 3D matrix. These molecules located in the interior of the proteins, in binding sites and /or superficial clefts, may act as bridges between separate elements of the protein matrix and thus participate to its structural plasticity; in some cases water also fills empty spaces in the interior of the proteins like polar or hydrophobic cavities and this regulates the protein internal compressibility and breathing dynamics; internal water may create specific transport pathways for ions and protons as in the case of membrane proteins and enhances locally the electrostatic field in such a way to facilitate charge separation processes and enzymatic activity. Structural alignment shows that the pools of water molecules detected in the interior of proteins are an evolutionary conserved element to be considered on the top of amino acids conservation paths. Structural water has been also indicated as a possible source of thermal resistance for a special class of proteins: the thermophiles.
While X-Ray captures only static information on the protein hydration, basically reporting on the probability that a spatial site is occupied by a water oxygen, other techniques may access the motion of hydration water more directly.
In particular O17 MRD experiments helped to determine the timescale of the exchange
dynamics of the so-called structural waters with the bulk solution [2]. MRD suggests that this class of water molecules, a few in the case of globular proteins, penetrates and escapes from the interior of the protein in the nanosecond time scale or longer. This slow water dynamics correlates to the protein conformational motion and to internal protein permeability. The seminal works on this topic from Halle and coworkers date back to the nineties and contributed to stimulate my passion for the study of protein hydration [3]. As young undergraduate student I walked my first steps in the field of protein simulations targeting the problem of hydration dynamics. Water exchange dynamics can naturally be followed along a MD trajectory. My work on the hydration of Lysozyme [4] was one of the first to directly monitor the exchange dynamics of internal water molecules in the nanosecond timescale, correlating this exchange to large
conformational rearrangement and gating. We provided a spatial visualization of the process accessed by MRD experiments and we suggested that the exchange dynamics might involve protein locations others than to those photographed by X-Ray.
The hydration layer
The dynamics of protein hydration is a complex process since it involves also a large number of molecules solvating the “external” protein surface [4]. These molecules experience a very different exchange dynamics. This dynamics can be seen as a “kiss and run” process: water enters in the hydration shell of the protein, interacts locally with the surface by forming h-bonds or simple contacts, and leaves afterwards the hydration shell. In general only few protein sites are visited during this “binding”. The characteristic time for the exchange depends on the local energetic/topological disorder of the protein surface. In average the 90% of hydration water exchanges within tenths of ps, for approximately a 7% of water, that may partially penetrates superficial clefts, the exchange stretches up to hundreds of ps. The resulting labile nature of the hydration shell and its response to external parameters (i.e. temperatures, pressure, presence of co-solutes) has an impact on the local and global flexibility of the protein matrix (locally and globally).
The average dynamics of protein hydration can be studied experimentally using O17 MRD technique, dielectric relaxation, light scattering (LS) [1]. For globular proteins the reorientational dynamics of water at the protein surface is only weakly retarded with respect to bulk, NMR and LS estimate a retardation factor of 3÷7. The analysis of my simulations confirmed this picture: I showed that by computing the average water reorientational dynamics in the hydration shell of the protein, the average retardation factor is of about 3÷6 depending on the definition of the shell [5]. A very similar retardation is also computed for the translational dynamics. Thus at the protein surface, as in a pure aqueous solution at ambient temperature, the average rotation and translation are intimately coupled since they both depend on the local h-bond breaking/forming mechanism. Different water models were tested and the same results were obtained.
The average behavior of water dynamics is completely determined by water residing in the hydration shell for less than a nanosecond. Indeed the small set of water molecules that
exchanges with longer times do not weight much on the averaging [6]. This result is in agreement with the interpretation of dielectric relaxation experiment proposed by Oleinikova et
al. [7].
The picture of a labile hydration layer characterized by a weak retarded dynamics contrasts the early interpretation of femtosecond experiments [8]. In this experiments the fluorescence kinetics of tryptophan amino acids is measured after photo-excitation. Solvent reorganization surrounding the excited chromophores contributes to the excited state decay. In the case of a protein, a fast and a slow timescales were extracted and interpreted in term of a separate contribution from free and strongly bound water molecules in the hydration shell. However, this model was severely challenged in recent years: the slow component is indeed caused mainly by the motion of the protein atoms and not by bound water molecules [9].
Figure. 1:
Dynamics of hydration water at the surface of the protein Lysozyme. Top Panel. The survival probability Nw(t) counts how many water molecules that are in the hydration shell of the protein at T=0 stays continuously in the shell up to time T=t. The function decay is well described by three time scales, see table on the left. Bottom Panel. Average rotation and translation dynamics of water in the protein hydration shell. The retardation with respect to the bulk dynamics is about 3÷6,
depending on the thickness of the hydration shell. The retardation for the rotation and translation are the same, indicating a coupling between the two dynamics.
The effect of disorder
Water dynamics near a protein surface differ from bulk not only quantitatively but also qualitatively. For instance the water reorientational correlation function computed from MD simulations does not exhibit a single exponential decay but rather a stretched exponential form:
!
c(t) " exp(#(t /$)%) [5]. Moreover, the mean square displacement computed for water in the
protein hydration shell is not linear in time but shows a sub-diffusive behavior:
!
r(t) " r(0)2 # t$, with α<1. Experimentally traces of this anomalous dynamics are visible in the intermediated scattering function used for extracting the dynamics of water at protein surfaces [10].
The origin of such an anomalous dynamics has always intrigued me since several theoretical models may serve for the explanation. But theoretical models must be “translated” in the specific context of protein hydration.
Let us start the discussion considering the translational motion. Two different models are usually invoked to explain water subdiffusity at a protein surface [11]. The first model describes the translational displacement as a Continuous Time Random Walk (CTRW) process [12], i.e. a Brownian diffusion model with a distribution of waiting times between two consecutive steps following a power-law
!
"(#) $ #%&. Such distribution leads to subdiffusive dynamics when 0<ν<2 [12]. In the context of protein hydration, the distribution of waiting times results from the disordered energetic landscape for the protein/water interaction and this depends on the chemical heterogeneity of the protein surface. The second possibility to explain the presence of subdiffusive dynamics is a change in the dimensions of the space explored by translation. It has been shown that a random walk occurring in a fractal space (topological disorder) can also lead to a subdiffusive behavior [13].
In order to probe the effect of topological and energetic disorders I designed an ad hoc in silico experiment. I considered the hydration dynamics around a static protein. This dynamics was investigated for two models, in the first one all the electrostatic interactions between the protein and water have been switched off, in the second model all the interactions were restored. The
water perceives only the geometrical disorder of the artificially whole “hydrophobic” protein surface. The second model represents a reference state for a static energetic/geometric disorder to be compared to the dynamical energetic/geometrical disorder that acts in a real system. It is clear from our results that for a static protein both the disorders contribute to the anomalous translational dynamics [6]. Comparison with a dynamical system indicates that protein dynamics reduces this effect mainly enlarging the dimension for the translational motion of water at the surface. It must be pointed out that the energetic disorder has not only an effect on the local interaction between the amino-acids and water, i.e. the possibility to form h-bonds. The distribution of polar and charged amino acids selects also the length scale of the hydrophobic interaction. Hydrophobic patches at protein surface are generally small in size and contoured by polar/charged amino acids. This distribution influences the orientation and the local packing of water avoiding extended dewetting that instead characterizes hydration of flat nanoscaled hydrophobic surfaces. In other words, the energetic disorder acts back on the geometrical disorder by altering the preferential orientation and connectivity of water at the surface. Recently, I have shown that this particular effect characterizes water behavior in concentrated solutions of small amphiphiles [14]. This work accomplished by G. Stirnemann during his PhD thesis showed that at high solute concentration anomalous water diffusion is observed and this can be explained only if both the geometrical disorder of the confining solutes and their energetic interactions with water are considered together. These systems are of practical interest since they are used experimentally to gather information on the hydrophobic hydration.
Figure 2:
Effect of topological and energetic disorders on hydration dynamics. Lys-T indicates the simulations of Lysozyme in water, Lys-F indicates the rigid protein, Lys-VdW indicates the rigid lysozyme with no electrostatic interaction with water.
We turn the attention to water reorientation in the hydration shell. It was appreciated in many computational studies that this relaxation process is not described by a single exponential function. In order to extract the characteristic time for the decay a stretched exponential fit is generally used and demonstrated to perform extremely well. The stretched nature of the correlation function decay suggested that the average reorientation of water in the hydration shell results from a broad distribution of independent kinetics. Water molecules are thought to reorient with different characteristic times depending on the local environment. Geometrical and energetic disorders can again be invoked to explain the presence of different reorientational channels, each characterized by an exponential decay. However, a stretched exponential decay results analytically from a well-defined probability distribution of the characteristic times. Reconstruct such a distribution is a challenging issue and will help to understand whether or not the stretched nature of the reorientational dynamics is simply a fit shortcut or it can be traced back to the specific protein surface chemical composition. Thanks to the collaboration with D.Laage we are now in position to give an answer.
D. Laage and J.T. Hynes introduced few years ago a model for describing water reorientation [15]. According to this model, Extended Jump Model, water reorientation can be monitored considering the time evolution of the OH bond orientation. The OH bond mainly reorients because of a hydrogen-bond exchange event, and this exchange is associated to a sudden large amplitude angular jump. The mechanism can be fruitful seen as a chemical reaction with a specific transition state, a free energy barrier and kinetics constant. The characterization of the transition state in term of intermolecular distances between the molecules entering in the reaction allows to evaluate how the jump mechanism is perturbed when occurring in proximity of a solute (h-bond acceptor or donor, or hydrophobic in nature). I have given a contribution to develop a model that accounts for the asymmetry of the reaction when this involves the reorientation of a water molecule initially forming an h-bond with an acceptor group and forming a h-bond with another water molecule in the final state of the jump reaction [16, 17]. I successfully tested the Jump Extended Model framework against amino acids and protein
the probability distribution of the reorientation events occurring in the hydration layer of the protein. These events were characterized depending on the proximity/binding to amino acid individual groups (polar, charged, hydrophobic, or in another language h-bond donor, acceptor and hydrophobic). The manuscript describing the main result of this research is currently under preparation. I anticipate here that the reconstructed probability is very different from the analytical form underlying a stretched exponential decay. Therefore the stretched exponential nature of the reorientational correlation function appears as just a convenient fit for extracting quantitative average decay time. However, it is also clear that the non-exponential decay is still related to the multiscale dynamics of the reorientation. This multi-scale dynamics can be easily understood in term of local topology and energetic disorder of the protein surface by considering the properties of the transition state of the jump event. The approach was also applied to the hydration of DNA in order to study water dynamics in the DNA minor and major grooves. P. Marquetand, previous post-doc at ENS, carried out this work under my supervision. We have continued the collaboration and the research is almost accomplished.
Figure 3: Left. Distribution of the second-rank characteristic time t2 evaluated using the EJM and computed for
water in proximity of acceptor, donor and hydrophobic sites. The distribution exhibit a Gaussian character stretched a long time by a power law tail. See inset fit. Right. Decomposition of the distribution of the jump time for the h-bond exchange event for water molecules h-bond to acceptor and donor group and in proximity of hydrophobic group, respectively.
The Skin of the protein
The chemical composition of a protein surface and its hydration control the interactions with other biomolecules. For instance large hydrophobic regions drive protein assembling. Specific location of arginines favors protein/DNA binding. Antifreeze proteins destabilize ice nucleation via large hydrophobic exposed patches.
In recent studies it was appreciated that protein thermostability can be increased via supercharging the surface. This finding is consistent with the well-know fact that thermophilic proteins (proteins from organisms that usually thrive at extreme thermodynamics conditions) are enriched in charged amino acids and show in average an higher number of salt-bridges with respect to their mesophilic homologous [18].
In recent years I approached the problem of protein thermostability paying specific attention to the coupling between water structure/dynamics and protein surface [19, 20]. I firstly appreciated that an important contribution to protein resistance to thermal perturbation comes from the protein surface and the coupling to the solvent. This finding is in contrast with the common view that links protein stability to internal packing. Comparing systematically three homologues proteins from a mesophilic, a thermophilic and hyperthermophilic organism I could see that going from the mesophile to the hyperthermophile the main differences between the three species were: an increased exposed surface; an increased number of protein/water h-bond density, an increased resistance of the water h-bond connectivity around the protein surface. This especial coupling seems indicating that water around a hyperthermophilic protein forms a resistant skin that is pinned to the protein surface through a larger number of h-bond. This skin could accommodate large protein motion activated by high temperature without inducing drastic water penetration in the protein core that would destroy the protein matrix. Therefore a stable and largely connected water h-bond network at the protein surface may be functional for dissipating the thermal excitation of protein internal degrees of freedom.
2
Micelles
Detergents are relatively short polymers owning amphiphilic character: they are constituted by a hydrophobic tail and a hydrophilic head [21]. Detergents form, in water solution and above a critical concentration (critical micelle concentration -cmc), micelles of different shape, size and size distribution. The self assembling of this class of molecules is guided by hydrophobic
In this paragraph I will shortly present my research on micellar systems. Two facts motivate my interest for these self-assemblies. First, the key forces that drive the self-assembling process are ubiquitous in biological systems. Namely, the “antagonism” between hydrophilic/hydrophobic interactions may be considered as the “universal” fuel of biological activity. Secondly, micelles are intrinsically bio-mimetic. They are routinely used for solubilize membrane proteins, are employed as models for studying peptide/membrane interactions, drug-delivering strategy and protein conformational switch. My work on these systems started when I was student in the Physics Dept. at the University of Rome. Later, along the years I continued independently my research on this topic: I chose micelles as my personal training system for understanding interfacial phenomena like the dehydration, confinement and shape-transition.
interactions: a micelle can be view as an oil core formed by the hydrophobic tails separated and screened from water by an interface constituted by the detergent hydrophilic heads, Fig. 4. The phase diagram of a detergent-water solution is very complex and depends on thermodynamics parameters like temperature and pressures, pH and on the hydrophobic to hydrophilic ratio of the detergent primary structure. Moreover detergents can differ depending on the nature of the head group: ionic, non ionic or zwitterionic.
In order to exploit such systems, i.e. in oil recovery processing, drug delivering, protein solubilization, it is essential to understand the microscopic effect of those parameters by focusing on the two sub-environments that characterize a micelle: the oil core and the interface. In my research I used MD simulations for studying the mentioned problem on the specific case of the CiEj surfactant family.
Figure 4:
A spherical micelle of C12E6. Left. Density
profile as a function of the distance from the center of mass of the aggregate.
The oil core of micelles
Firstly I want to discuss how the properties of the micellar oil core change as a function of the size of the hydrophilic head and of the thermodynamic parameters T and P. In one of my first works I compared models of spherical assemblies formed by molecules owning a hydrophilic
head of different length: oil droplet of dodecanes (no hydrophilic head), micelle of dodecan-1-ol (small hydrophilic head constituted by a hydroxyl group) and C12E3 and C12E6 micelles
(extended hydrophilic chain Ej with j=3,6) [22]. As expected we showed that increasing the
extension of the hydrophilic chains the screening of the oil core to water increases as well. As consequence of this screening the effective pressure acting on the oil core, and due to the hydrophobic interaction, is reduced. This induces important changes. For instance we found a direct correlation between the extension of the hydrophilic chain and the increased flexibility and fluidity of the hydrocarbon tails confined in the core. This result is of interest in the context of drug loading since the confinement of a small hydrophobic molecule in the interior of a micelle could be tuned by changing the extension of the hydrophilic moiety. Moreover the size of the hydrophilic head results a key parameter for understanding the effect of thermodynamic parameters as we will discuss below.
The properties of the oil core have been indicated as the cause of the uncommon shape transition observed in a C12E5/water solution under high pressure (3kbar). Performing SANS
experiments Bossev et al. [23] reported that branched and semiflexible cylindrical micelles, stable at ambient pressure, transform into a bundle of ordered not-branched cylindrical micelles upon applying external pressure. This transition was traced back to oil core freezing. Other SANS experiments [24] performed on C8E5/watter solution under high pressure reported for
spherical micelles the collapse and dehydration of the interface but not core freezing. Inspired by this experimental results I performed a systematic study on a C12E6 micellar system at
pressures varying in the interval [0.001,3] kbar [25]. The simulations reproduced the interfacial dehydration observed experimentally and that is caused by the collapse of the extended hydrophilic chains toward the core. As effect of the high pressure the rigidity of the alkyl chains is increased as it was observed in a solvated oil droplet that is characterized by a pseudo crystalline chain packing. However, the core does not freeze at the simulated pressures since no signature of dynamical arrest was measured. Probably the ratio of alkyl/hydrophilic chain length plays a major role in defining the pressure and the temperature for core freezing. It is well known that shorter alkyl chains freeze at higher pressure, and we have observed that for a given alkyl chain length the extension of the hydrophilic moiety do contribute to the alkyl flexibility under micellar confinement. While the oil core in C12E5 is found to freeze at 3 kbar, in a
C12E6 the freezing pressure might shift at higher value due to the different compressibility of the
interface.
Finally let’s focus on the effect of temperature and in particular on the sphere-to-rod transition driven by temperature increase. Ben Shaul and coworkers [26] have quantified the alkyl intrachain entropic contribution to micelle stability and thermodynamics in different geometry and correlated it to micellar shape transition. Our results show that for a given spherical shape this entropic contribution varies by tuning the extension of the hydrophilic chain and increasing temperature or pressure [22, 25, 27]. However, I did not find any correlation with the geometry of the confinement [28]. Even if going from a spherical to a cylindrical shape the oil core density decreases in very good agreement with mass density measurement (see Figure 5), the alkyl chains sample the same conformational space. This finding suggests that the alkyl entropy gives only a minor contribution to the sphere-to-rod transition. On the contrary as I will discuss right below, the internal entropy of the hydrophilic chains results very important.
Figure 5: Sphere-to-Rod transition monitored by change in the volume of the alkyl tails. The experimental data are from density experiments, the volumes from the simulations of the spherical micelle are reported in red and the volumes from the simulations of the cylindrical micelle are reported in blue.
The Interface: Dehydration and shape transition
In this paragraph I will shift the attention from the oil core to the interfacial region of the micelles. In this extended region three phases mix: the hydrophobic surface of the oil core exposed to water, the extended Ej units that folds in α-helix and water. Since the Ej heads are not uniformly
distributed in the interface, water may experiences three different sub-environments: i) lay on the hydrophobic core that is not completely screened, ii) be trapped between the Ej fragments
and iii) be bulk like.
The mixture of these sub-environments influences the response of a micelle to thermodynamics perturbation like temperature and pressure increases, and could be connected to shape transition.
Following the innovative strategy of chemical trap experiments designed by Romstead and coworkers [29] I tried to understand at microscopic level the dehydration phenomena induced by temperature increase. In a chemical trap experiment the amount of water in a micellar interface can be evaluated locally by monitoring the reactivity of a chemical probe attached to a hydrocarbon tail and captured in the micelle. I first studied the dehydration process for spherical micelles and found, in excellent agreement with the experiments, that dehydration occurs only in the internal part of the interface, mainly involving those water molecules in direct contact with the oil core. Here water forms a h-bond network that spans locally the hydrophobic surface and pins to the oxygen of the most internal E unit of the hydrophilic heads. When temperature increases these networks disconnect and only water linked to the E units persist in the internal interface [30]. In average, raising the temperature from 10° C to 45° C 1-2 molecules per E unit “evaporate” toward the bulk [27]. Dehydration appears as the results of a structural reorganization of the internal part of interface that mainly modifies the coverage of the hydrophobic patches of the core. This process is not associated to a specific change in the
dynamics which both follow the same trend of a pure water solution. It is worth to mention that temperature has a minor effect on the hydration of the E units.
Experimentally it is well known that upon temperature increases micelles undergo a shape transition, from spherical to cylindrical shape. Using atomistic simulations is difficult to reproduce such a process since a very large system composed of several spherical micelles allowed to fuse and to form a finite size cylinder must be simulated a different temperature and for long time. Therefore simplified coarse-grain models are the good choice for an extended investigation of this transition. In my work I used only atomistic models and therefore I limit myself to steady micelles, either spherical or cylindrical, and I systematically compared the results at different temperatures in order to understand how the changes in the interface could influence the process [28]. The main result of my work is that in cylindrical packing the hydrophilic chains mainly loose their α-helix fold, they bend towards the oil core hence increasing the screening to water. The surface per monomer exposed to water of the oil core decreases of a factor 2 going from a spherical geometry to the cylindrical one. This corresponds to a free energy change of about 2.5 kbT. The optimal screening in the cylindrical packing is
guarantee by the increased disorder of the E fragments that therefore represent an entropic reservoir for the transition. The temperature dehydration associated to the shape transition can be estimated to 1.5 water molecules per monomer in excellent agreement with experiments. As mentioned in the previous paragraph the collapse of the hydrophilic heads toward the core characterizes the response of a micellar system under high pressure. Increasing the pressure the E chains get partially compressed and tend to fill the innermost part of in the interface. As consequence the water molecules are partially expelled and dehydration occurs. It is interesting to note that around a pure hydrophobic surface (flat or spherical) when pressure is increased water tend to approach the surface, in a micelle the hydrophilic heads compete with the solvent compressibility and oppose to the filling of the innermost layers by the solvent.
Figure 6: Dehydration of a spherical micelle induced by temperature increase. Left. Water per E unit in concentric hydration shells as a function of the distance from the CM of the micelle. Hydration at T=10°C is reported in black, hydration at T=45°C in red. Dehydration occurs in the internal shells and is in agreement with chemical trap experiment. Right. Pictorial view of the h-bond network formed by water at the surface of the oil core. The network is linked to the innermost E units of several chains.
3
Energy storage & conversion
The ante-fact: photosynthesis.
A part of my PhD research was devoted to the investigation of a photosynthetic protein. Namely I focused on the early step of photosynthesis occurring in bacteria. This process proceeds via a photo-stimulated electron transfer (ET) between a set of chromophores embedded in a membrane protein: the reaction center (RC). RC is a membrane protein characterized by high structural C2 symmetry with respect to the membrane axes. The cyclic ET across the protein
In this last paragraph I will present my works on systems and materials relevant for energy storage and conversion. This line of research started during my first post-doc and allowed me to acquire expertise in the field of quantum simulations. My research required both methodological and code development in the specific field of quantum/classical and ab initio MD. Specifically I have studied the optical properties of organic semiconducting polymer and the hydrogen storage and release mechanism in alanates.
generates a gradient of protons trough the membrane and this drives the synthesis of ATP for storing the solar energy in chemical form.
Despite the overall structural symmetry the ET occurs only on one branch of the protein and it is not yet clear the origin of such a functional symmetry break. In my research I investigated the influence of the protein environment on the ET by combining classical MD and the framework of the Marcus theory. From the computational point of view my work allowed to compute the parameters entering in the Marcus’s reaction rate constant including explicitly the contribution of the electronic polarization [31]. Notwithstanding the huge load of work the results I obtained were unsatisfactory since I could not extract any microscopic definitive signature of the functional asymmetry. It is not yet clear to me if the main limitation of my study was due to the particular model employed for describing the system (i.e. the classical Force Field) and/or the sampling procedure I used for accounting electronic polarization effect. For instance one may suppose that the asymmetry of the electron transfer would originate from the initial asymmetric charge distribution of the photo-excited chromophore (the special pair P) or from an asymmetric electronic coupling between this chromophore and the other redox sites located in the two branches of the proteins. However, at that time, the calculation of the excited state charge distribution of the chromophores or their coupling in the protein matrix was just unfeasible. Similarly polarizable FFs were under development and not currently used to sample the conformational motion of large biomolecules. Hence I applied a polarizable Hamiltonian a
posteriori on the trajectories generated by classical MD.
At the end of my PhD I was firmly motivated to acquire competence in the field of quantum simulations. This motivation drove me to Austin, Texas as a post-doc in the group of P.J. Rossky.
Semi-conducting Polymers
Conjugated polymers (CP) possess the important optoelectronic properties of semiconductors [32]. A new class of devices such as organic light emitting diodes (OLED), photovoltaic cells, transistors, and flexible displays have been conceived and produced from this class of polymers. However, the general usefulness of such technological devices depends on the
competitive cost of engineering and production and on their efficiency. The former aspect is guaranteed by the low cost and flexibility of the plastic material manufacturing, whereas the latter is currently compromised by the consequences of electronic interactions occurring between the polymer chains assembled in the thin films constituting the devices. As a result there is great interest in understanding the fundamental interactions and processes occurring in such films.
A computational method to be effective for treating these processes must treat the system at the quantum level, it must consider the dynamics of the excite states and its coupling with the nuclear motion and must included environmental effects at some level of theory.
For this purpose, in collaboration with P.J. Rossky I developed and implemented a mixed quantum/classical method that allows to study the dynamics of π-conjugated polymer in ground and electronic exited states in both gas phase and solution [33]. The method couples the molecular mechanics model QCFF/PI [34] originally developed by Karplus and Warshel and a semiempirical model for the π-system described at the level of the PPP (Parisier-Parr-Pople) Hamiltonian [35] [36]. The dynamics on the exited states was based on the configuration interaction method; non-adiabatic transitions between electronic states were accounted using the stochastic surface-hopping technique. The code developing was extremely time consuming: I spent almost one year in coding and debugging and testing. As final achievement I mention that my code is currently used by the group of Prof. P.J. Rossky for advancing the understanding of organic electronics.
The method was firstly tested against isolated chains of PPV in gas phase [33]. We reproduced very well the spectral properties of the system and their dependency on the polymer length. At variance with the common planar representation of CPs our detailed investigation of PPV oligomers in ground and excited state firstly revealed that π-conjugated polymers subjected to thermal disorder are quite flexible and deviate from the full planar configuration. Only a subset of adjacent polymer units retains a relative planar orientation and this explains the characteristic saturation effect observed in absorption spectra as a function of the polymer length. In fact the energy gap between the ground state and the first optically active state becomes independent on the overall polymer size, meaning that the π-conjugation extends only on a finite number of
polymer units, i.e. 6÷7 for PPV. Thus our simulations have shows that the thermal disorder may be at the origin of the finite conjugation length observed in such systems.
Thanks to the developed model we were also able to investigate the electronic dynamics in excited states [33]. We observed that following the photo-excitation the generated exciton (electron/hole pair) gets trapped in the middle of the chain. This localization that, can be monitored by the distortion of the CC bond length along the chain, occurs in a few hundreds of femtoseconds and is driven by the alternate exchange of energy between single and double bonds in the phenyl rings and the vinylene junctions. Once equilibrated the exciton fluctuates along the chain around its local trap. This motion causes a slight asymmetry of the emission spectra that shows a shallow shoulder red-shifted with respect to the main peak.
Figure 7. Panel A. Absorption and emission spectra of an isolate chain of (10)PPV. Panel B. C-C bond length change upon photo-excitation along the (10)PPV chain for the vynylene junctions and the phenyl rings. Panel C. Time evolution of the overall bond length distortion due to photo-excitation as a function of time for junctions (ΔDJ)
and the rings (ΔDR).
As a second step the method was applied to stacked chains of PPV [37]. This configuration mimics the packing of chains in the thin film. As known from previous theoretical works and as a consequence of selection rules the first optically accessible electronic state in perfectly aligned π-stacked chains is S2. However, in a simulation at finite temperature the two stacked chains
experience a configurational disorder that makes S1 optically active as well even if the oscillator
strength for the S0S1 transition remains small.
