Etude de systèmes moléculaires complexes Développement d'outils de modélisation moléculaire à basse résolution Laurence Leherte Laboratoire de Physico-Chimie Informatique (PCI) Groupe de Chimie Physique Théorique et Structurale Séminaire résidentiel de la Faculté des Sciences des FUNDP « Les systèmes complexes » Blankenberge, Janvier 2009
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Etude de systèmes moléculaires complexes
Développement d'outils de modélisation moléculaire à basse
résolutionLaurence Leherte
Laboratoire de Physico-Chimie Informatique (PCI)Groupe de Chimie Physique Théorique et Structurale
Séminaire résidentiel de la Faculté des Sciences des FUNDP« Les systèmes complexes »Blankenberge, Janvier 2009
All-atom description of a moleculeHuge number of degrees of freedomMultiple minima problem
I. Reduced Molecular Representations
All-atom model Coarse-grain model
Coarse-grain modelsCα Center-of-mass
Cα representation of lysozyme (green spheres). Interactions are represented by springs (red).[K. Hinsen, http://dirac.cnrs-orleans.fr/plone/Members/hinsen/elastic-network-models-for-proteins, 2007]
[Basdevant et al., J. Phys. Chem. B 111 (2007) 9390]
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Coarse-grain models Uses (1)
Lowest frequency normal mode of adenylate kinase obtained with elastic network normal mode analysis [http://ctbp.ucsd.edu/summer_workshop04/elastic_network/html/elastic_network.htm]
Slow & large amplitude dynamicsNormal Mode Analysis
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Coarse-grain models Uses (2)
Open-to-closed transition of adenylate kinase [Chu & Voth, Biophys. J. 93 (2007) 3860 ]
Conformational changes in proteinsElastic Network Models
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Time-dependent trajectoriesMolecular Dynamics
Coarse-grain MD simulation (350 ns) of Kv channel embedded in a lipid bilayerhighlighting the overall conformational rearrangement of the model during theclosing process [Treptow et al. J. Phys. Chem. B 112 (2008) 3277]
Coarse-grain models Uses (3)
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Coarse-grain models Uses (4)Protein docking
Prediction of the configuration of molecular complexes
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[Becue, A. Development of an original genetic algorithm method dedicated to complementarity studies between protein-protein and protein-nucleic acid macromolecular partners, PhD Thesis, FUNDP, 2004]
- Coarse-grain force constant ~ ED overlapintegral
- Justification of commonly used rc cut-offvalues
- Lowest limit for force constants smoothing of the B profile
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V. Electrostatics of Proteins
Determination of protein coarse-grain charges from smoothed electron density distribution functions and molecular electrostatic potentials[Leherte & Vercauteren, accepted in Computational Chemistry: New Research, NovaPublishers]
Construction of Gly7-AA-Gly7 in a β conformation withvarious AA rotamers