SBIR Phase I: Mutable Molecular Surface

*96-60164康诺利这个小型企业创新研究第一阶段项目将开发计算方法，当分子改变其构象时，动态重新计算溶剂可访问的分子表面。耶鲁大学的弗雷德·理查兹将溶剂可及的分子表面定义为蛋白质分子周围的光滑包膜。它被发现在研究蛋白质-蛋白质和药物-蛋白质结合方面是有用的。目前计算这个表面的方法会重新计算整个表面，即使只有部分原子移动。仅为已改变的区域重新计算表面将导致计算时间的极大节省，并将允许交互式分子显示系统的用户改变蛋白质构象并观看表面被近乎实时地重新计算。应用包括(A)蛋白质同源模型的建立，(B)蛋白质工程中的定点突变，以及(C)晶体结构的不确定性，其中存在表面氨基酸侧链的几种可能的取向。***

*** 96-60164 Connolly This Small Business Innovation Research Phase I project will develop computational methods for dynamically recomputing the solvent-accessible molecular surface as the molecule changes its conformation. The solvent-accessible molecular surface has been defined by Fred Richards of Yale University to be a smooth envelope surrounding a protein molecule. It has been found to be useful in studying protein-protein and drug-protein binding. Current methods for computing this surface recompute the entire surface even if just some of the atoms move. Recomputing the surface for just the region that has changed would result in a great savings in computation time and would allow a user of an interactive molecular display system to alter the protein conformation and watch the surface be recomputed in near real time. Applications include (a) protein homology model building, (b) site-specific mutagenesis in protein engineering, and (c) crystallographic structural uncertainty, where there are several possible orientations of a surface amino acid side chain. ***