Development of coarse grained simulation models to study structure formation and self assembly in peptide systems

• Applicant: Professorin Dr. Christine Peter
• Subject Area: Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
• Term: from 2008 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 76490208

• Final Report Year: 2015

Final Report Abstract

We have developed multiscale simulation strategies that are suitable for peptide (and other biomolecular) systems in aqueous media, focusing on methodologies that derive interactions between CG particles in a systematic bottom-up fashion from an underlying atomistic model. We have studied peptide systems that self-assemble and form nanostructures, mostly targeting at applications in the context of biological and biomimetic materials. For the first model system – very short amphiphilic dipeptides that aggregate in solution and form nanostructures – we have adapted and extended the coarse graining methods that had originally been developed for synthetic polymers to peptide-specific questions. We have developed a new method to determine non-covalent interactions between CG particles that yield the correct thermodynamic association behavior and reproduce the solvation structure around the peptide molecules. For the second model system – short oligo-alanine peptides, that are relevant elements in nanocrystalline parts in biological fibers such as spider silk – we have investigate in more details the conformational properties of a peptide chain on the CG level and extended the above methodologies. The third model system was a class of amphiphilic peptides that form highly structured β-sheet aggregates at an air/water interface. Here, we could combine the developments made for the other two systems and add aspects regarding interface and partitioning properties of CG models. We have extended the coarse-graining methodology to inhomogeneous systems. This new method allowed us to adjust the balance between local liquid structure, interface thermodynamics, and the partitioning of solutes. Overall our CG model development had a strong methodological component. We have investigated thermodynamics and structures obtained with different types of CG models and different methods to parameterize CG interaction functions. In recent years, methodological questions regarding the representability and transferability of CG interaction functions have been recognized as particularly relevant. We have investigated the representability of conformational states by CG models, and the transferability of the CG interaction functions to different state points or local environments of the molecules. The group has contributed to the understanding of concentration transferability in hydrophilic/hydrophobic mixtures and in electrolyte (and polyelectrolyte) solutions, as well as of phase-separation and phase-transition phenomena. Representing environment-induced conformational transitions, e.g. folding processes that are induced by a change in environment of a peptide or protein molecule, is still one of the major challenges for multiscaling in biomolecular systems and one of the key issues for both folding and aggregation studies. Addressing these questions remains a major focus of our group. In the multiscale simulation framework, the atomistic level of resolution (from which the CG models are developed and to which one can come back after reinserting atomistic coordinates into CG structures) is highly relevant to compare results to experimental data. Especially in the field of biopolymer/mineral systems we had successful collaborations with experimental partners – both external as well as local collaborators at the University of Konstanz – which we will extend and intensify.

Publications

• ”Multiscale simulation of soft matter systems from the atomistic to the coarse-grained level and back”, Soft Matter , 5 , 4357, 2009
  C. Peter, K. Kremer
  
• ”Self-assembling dipeptides: including solvent degrees of freedom in a coarse-grained model”, Phys. Chem. Chem. Phys., 11 , 2068, 2009
  A. Villa, N.F.A. van der Vegt, C. Peter
  
• ”Transferability of Nonbonded Interaction Potentials for Coarse-Grained Simulations: Benzene in Water”, J. Chem. Theory Comput., 6, 2434, 2010
  A. Villa, C. Peter, N.F.A. van der Vegt
  
• ”A Challenge for Peptide Coarse Graining: Transferability of Fragment-Based Models”, Macromol. Theory Simul., 20, 451, 2011
  O. Engin, A. Villa, C. Peter, M Sayar
  
• ”Transferability of coarse grained potentials: implicit solvent models for hydrated ions”, J. Chem. Theory Comput., 7, 1916, 2011
  J.-W. Shen, C. Li, N.F.A. van der Vegt, C. Peter
  
• ”Coarse-Grained and Atomistic Simulations of the Salt-Stable Cowpea Chlorotic Mottle Virus (SS-CCMV) Subunit 26–49: β-Barrel Stability of the Hexamer and Pentamer Geometries”, J Chem Theory Comput, 8,3750–3758, 2012
  Bereau, Tristan; Globisch, Christoph; Deserno, Markus & Peter, Christine
  
• ”Multiscale simulation of peptides: Consistent conformational sampling in atomistic and coarse-grained models”, Comput. Chem., 33, 937–949, 2012
  Bezkorovaynaya, Olga; Lukyanov, Alexander; Kremer, Kurt & Peter, Christine
  
• ”Structure-based coarse-graining in liquid slabs”, J Chem Phys, 137, 064102, 2012
  Jochum, Mara; Andrienko, Denis; Kremer, Kurt & Peter, Christine
  
• ”A transferable coarse-grained model for diphenylalanine: How to represent an environment driven conformational transition”, J Chem Phys, 139, 234115, 2013
  Dalgicdir, Cahit; Sensoy, Ozge; Peter, Christine & Sayar, Mehmet
  
• ”Molecular Dynamics Simulations of Peptides at the Air–Water Interface: Influencing Factors on Peptide-Templated Mineralization”, Langmuir, 30,15486–15495, 2014
  Jain, Alok; Jochum, Mara & Peter, Christine