Development of Implicit Solvation Potentials for Biomolecules

DBI 9974621，Lazarlane，Themis。纽约市立大学。发展隐含的solvation潜力的生物分子。项目总结生物大分子与溶剂的相互作用是至关重要的，它们的结构和功能，需要考虑到在计算机建模研究。到目前为止，这主要是通过模拟生物分子沿着大量的水分子来实现的。这种方法（显式溶剂化）有两个缺点：它是计算密集型的，并没有揭示所观察到的行为的热力学起源，因为自由能是不容易在模拟。解决这个问题（隐式溶剂化）的一个更有效的方法是在分子力学力场中加入一个溶剂化自由能的解析函数。这种功能的蛋白质在水中最近已经开发和添加到CHARMM力场，以获得近似的有效能量的蛋白质在溶液中（EEF1）。拟议的工作将继续在这条道路上，a）进一步测试和开发改进EEF 1，B）扩展模型到其他生物分子，如核酸，碳水化合物，脂质，金属和辅因子，c）扩展模型到其他溶剂，如变性剂溶液和非极性环境模仿生物膜，和d）纳入pH值，pKa位移和离子强度的影响。这项工作的目的是开发一套电位，可以准确地代表各种溶剂环境中发现的生命系统和生物分子的体外实验研究。新的潜力，实施到现有的或新的软件，将允许更大和更复杂的生物系统的研究比迄今为止。

DBI 9974621, Lazaridis, Themis. CUNY City College. Development of implicit solvation potentials for biomolecules.Project SummaryThe interaction of biological macromolecules with solvent is crucial to their structure and function and needs to be taken into account in computer modeling studies. Until now, this has been accomplished primarily by simulating the biomolecule along with a large number of water molecules. This approach (explicit solvation) has two drawbacks: it is computationally intensive and does not reveal the thermodynamic origins of the observed behavior because free energies are not readily available in the simulation. A more efficient approach to this problem (implicit solvation) is to add an analytical function for the solvation free energy to the molecular mechanics force field. Such a function for proteins in water has been recently developed and added to the CHARMM force field to obtain an approximation to the effective energy of proteins in solution (EEF1). The proposed work will continue on this path by a) further testing and developing improvements to EEF1, b) extending the model to other biomolecules, such as nucleic acids, carbohydrates, lipids, metals and cofactors, c) extending the model to other solvents, such as denaturant solutions and nonpolar environments mimickingbiological membranes, and d) incorporating the effects of pH, pKa shifts, and ionic strength. The objective of this work is to develop a set of potentials that can accurate represent the various solvent environments found in living systems and in experimental in vitro studies of biomolecules. The new potentials, implemented into existing or new software, will allow the study of larger and more complex biological systems than has been possible so far.