Computer Modeling and Theoretical Studies of Biopolymers

该计划涉及分子和随机动力学计算机模拟方法的开发和应用，以生物聚合物（蛋白质，碳水化合物和DNA）和脂质组件（膜和胶束）。 目前感兴趣的系统包括：肽与细胞膜和胶束的相互作用;和多糖疫苗的溶液构象。 发展了一种简单的方法，在恒压分子动力学（MD）模拟中考虑长程Lennard-Jones项。 这种远程校正包括一个额外的应用压力张量，这是定期计算的瞬时压力在选定的截止和一个很长的截止的差异。 它提供的结果是几乎独立的LJ截止距离在可忽略的额外计算成本，特别适合于各向异性系统，如液体/液体界面或异质大分子，其中基于球对称径向分布函数的近似预计会失败。 一篇描述这项工作的论文被《物理化学杂志》接受发表。 在胶束和脂质双层中对HIV融合肽进行了一系列分子动力学模拟。 计算表明，胶束中的肽的实验结果不一定适用于细胞膜，主要感兴趣的系统。 这些研究的结果不久将提交出版。 当使用CHARMM参数集C22时，预期为α螺旋的肽的广泛MD模拟产生π螺旋。 这一结果促使Feig、Mackerell和布鲁克斯开发了一个新的参数集C22/CMAP。对相同肽的后续模拟证实了C22/CMAP的有效性（即，α-螺旋是稳定的; π-螺旋恢复为α）。这些模拟和相关实验研究的结果不久将提交出版。

This program involves development and application of molecular and stochastic dynamics computer simulation methods to biopolymers (proteins, carbohydrates and DNA) and lipid assemblies (membranes and micelles). Systems of present interest include: interaction of peptides with cell membranes and micelles; and solution conformation of polysaccharide vaccines. A straightforward method that accounts for the long-range Lennard-Jones terms in constant pressure molecular dynamics (MD) simulations was developed. This long-range correction consists of an additional applied pressure tensor which is periodically calculated from the difference of instantaneous pressures at the selected cutoff and a very long cutoff. It provides results that are nearly independent of the LJ cutoff distance at negligible additional calculation costs, and is particularly suited for anisotropic systems such as liquid/liquid interfaces or heterogeneous macromolecules where approximations based on spherically symmetric radial distribution functions are expected to fail. A paper describing the work was accepted for publication in the Journal of Physical Chemistry. A series of molecular dynamics simulations of the fusion peptide of HIV were carried out in micelles and a lipid bilayer. The calculations indicated that experimental results for the peptide in micelles are not necessarily applicable to cell membranes, the system of primary interest. The results of these studies will shortly be submitted for publication. Extensive MD simulations of peptides expected to be alpha helical yielded pi-helices when using the CHARMM parameter set C22. This result motivated the development of a new parameter set C22/CMAP by Feig, MacKerell and Brooks. Follow-up simulations on the same peptides confirmed the validity of C22/CMAP (i.e., alpha-helices were stable; pi-helices reverted to alpha). The results of these simulations and related experimental studies will shortly be submitted for publication.