Comparison of reduced point charge models of proteins: Molecular Dynamics simulations of Ubiquitin  

作　　者：LEHERTE Laurence VERCAUTEREN Daniel P. 

机构地区：[1]Unité de Chimie Physique Théorique et Structurale, Laboratoire de Physico-Chimie Informatique, Namur MEdicine & Drug Innovation Center (NAMEDIC), Department of Chemistry, University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium

出　　处：《Science China Chemistry》2014年第10期1340-1354,共15页中国科学（化学英文版）

摘　　要：Reduced point charge models of amino acids are used to model Ubiquitin （PDB： 1UBQ）. They are designed （i） from local ex- tremum positions in charge density （CD） distribution functions built from the Poisson equation applied to smoothed molecular electrostatic potential functions, or （ii） from local maximum positions in promolecular electron density distribution （ED） func- tions. Charge values are fitted versus all-atom Amber99 molecular electrostatic potentials. The program GROMACS is used to generate molecular dynamics trajectories of the protein, under various implementation schemes, solvation, and temperature conditions. Point charges that are not located on atoms are considered as virtual sites with a null mass and radius. The results illustrate that secondary structure is best preserved with the CD-based model at low temperatures and in vacuum. This indi- cates that local potential energy wells are consistent with the all-atom model. However, at room temperature, the structure is best conserved when point charges are forced to be located on atoms, due to a better description of the Coulomb l-4 energy terms. The ED-based model, generated at a lower resolution, led to the largest discrepancies versus the all-atom case. The CD-based model allows the formation of protein-water H-bonds with geometrical properties similar to the all-atom ones. Con- trarily, intra-molecular H-bonds are not well described. Structural, thermodynamical, and dynamical properties of proteins modelled with reduced point charge models are also significantly affected by the choice of the solvent force field.Reduced point charge models of amino acids are used to model Ubiquitin(PDB: 1UBQ). They are designed(i) from local extremum positions in charge density(CD) distribution functions built from the Poisson equation applied to smoothed molecular electrostatic potential functions, or(ii) from local maximum positions in promolecular electron density distribution(ED) functions. Charge values are fitted versus all-atom Amber99 molecular electrostatic potentials. The program GROMACS is used to generate molecular dynamics trajectories of the protein, under various implementation schemes, solvation, and temperature conditions. Point charges that are not located on atoms are considered as virtual sites with a null mass and radius. The results illustrate that secondary structure is best preserved with the CD-based model at low temperatures and in vacuum. This indicates that local potential energy wells are consistent with the all-atom model. However, at room temperature, the structure is best conserved when point charges are forced to be located on atoms, due to a better description of the Coulomb 1-4 energy terms. The ED-based model, generated at a lower resolution, led to the largest discrepancies versus the all-atom case. The CD-based model allows the formation of protein-water H-bonds with geometrical properties similar to the all-atom ones. Contrarily, intra-molecular H-bonds are not well described. Structural, thermodynamical, and dynamical properties of proteins modelled with reduced point charge models are also significantly affected by the choice of the solvent force field.

关 键 词：molecular electrostatic potential electron density smoothing of molecular fields critical points point charge model PROTEIN UBIQUITIN 

分 类 号：O629.73[理学—有机化学]