title: Evaluation of reduced point charge models of proteins through Molecular Dynamics simulations: application to the Vps27 UIM-1-Ubiquitin complex.
abstract: Reduced point charge models of amino acids are designed, (i) from local extrema positions in charge density distribution functions built from the Poisson equation applied to smoothed molecular electrostatic potential (MEP) functions, and (ii) from local maxima positions in promolecular electron density distribution functions. Corresponding charge values are fitted versus all-atom Amber99 MEPs. To easily generate reduced point charge models for protein structures, libraries of amino acid templates are built. The program GROMACS is used to generate stable Molecular Dynamics trajectories of an Ubiquitin-ligand complex (PDB: 1Q0W), under various implementation schemes, solvation, and temperature conditions. Point charges that are not located on atoms are considered as virtual sites with a nul mass and radius. The results illustrate how the intra- and inter-molecular H-bond interactions are affected by the degree of reduction of the point charge models and give directions for their implementation; a special attention to the atoms selected to locate the virtual sites and to the Coulomb-14 interactions is needed. Results obtained at various temperatures suggest that the use of reduced point charge models allows to probe local potential hyper-surface minima that are similar to the all-atom ones, but are characterized by lower energy barriers. It enables to generate various conformations of the protein complex more rapidly than the all-atom point charge representation.
authors: Unité de Chimie Physique Théorique et Structurale, University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium. Electronic address: laurence.leherte@unamur.be.
authors: Laurence
authors: L
authors: Leherte
authors: Unité de Chimie Physique Théorique et Structurale, University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium.
authors: Daniel P
authors: DP
authors: Vercauteren
mesh_terms: D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000737:chemistry*; D055672:Static Electricity; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D011506:Proteins; D025801:Ubiquitin; D033921:Vesicular Transport Proteins
keywords: Critical points; Electron density; Molecular electrostatic potential; Point charge model; Protein; Smoothing of molecular fields; Ubiquitin complex