Computer Simulation of Protein Structure and Kinetics

9418964将开发用于表示多肽和蛋白质在溶液中的构象动力学的新的计算机模拟技术。这些技术将包括两个发展：使用过抑制约束朗之万动力学来表示多肽链的动力学，其中考虑了笛卡尔空间中的位置和多肽所有原子上的力；以及多肽与溶剂相互作用的表示的发展。Gronbech-Jensen和Doniach最近发表的过阻尼约束朗之万动力学，是通过投影力场的所有分量来获得的，这些分量往往会改变约束键的长度，从而改变肽主链和侧链上的键角。溶剂的处理将基于朗之万动力学方法来显式地研究水分子、它们彼此之间以及它们与多肽之间的相互作用，以及基于一种新的“平均场”方法来计算距离表面原子8埃的多肽的水化壳层。这些新技术将被应用于模拟小分子多肽链13到20个残基中的螺旋-随机卷曲转变，这些残基具有新生的螺旋性质。***

9418964 Doniach New computer simulation techniques for representing the conformational kinetics of polypeptides and proteins in solution will be developed. These techniques will comprise two developments: the use of overdamped constrained Langevin dynamics to represent the kinetics of a polypeptide chain, in which the positions in Cartesian space and forces on all atoms of the peptide are taken into account; and the development of the representation of the interaction of the peptide with solvent. The overdamped constrained Langevin dynamics, which has recently been published by Gronbech-Jensen and Doniach, is obtained by projecting out all components of the force field which would tend to alter constrained bond lengths, and hence, bond angles in the peptide backbone and side chains. The treatment of solvent will be based both on a Langevin dynamics approach to explicit water molecules, their interactions between each other and with the peptide, and on a novel "mean-field" approach to the calculation of the hydration shell of a polypeptide out to a distance of 8 Angstrom from the surface atoms. These new techniques will be applied to the simulation of the helix-random coil transitions in small polypeptide chains 13 to 20 residues which are known to have nascent helix properties. ***