Level-Set Variational Implicit-Solvent Approach to Biomolecular Interactions

描述（由申请人提供）：该项目开发了一个概念新颖的理论和强大的计算技术来研究水溶液中的生物分子相互作用。这种相互作用显著影响蛋白质折叠、分子识别和许多其他生物过程。这种相互作用的关键性质之一是毛细性蒸发或脱湿，它可以严重影响溶剂化自由能和生物分子结构。该项目的目标是更好地理解生物分子系统中的这种疏水相互作用，并为分子识别创建一个最先进的计算程序。

DESCRIPTION (provided by applicant): This project develops a conceptually novel theory and robust computational technologies to investigate biomolecular interactions in aqueous solutions. Such interactions influence significantly protein folding, molecular recognition, and many other biological processes. One of the crucial properties of such interactions is the capillarity evaporation or dewetting that can affect critically the solvation free energy and biomolecular structures. The goal of this project is to better understand such hydrophobic interactions in biomolecular systems and to create a state-of-the-art computational program for molecular recognition. The new variational model couples all the dispersive, non-polar, and polar interactions to local geometry in a free-energy functional. This theoretical model and the level-set numerical method can well describe the hydrophobic interaction and complex free-energy landscapes of biomolecular systems that are generally not correctly captured in established implicit-solvent models. Sophisticated numerical methods for electrostatics are developed to couple with the level-set method. Further model refinement to include solute molecular mechanics and stochastic effects can lead to a new computer program for molecular recognition that will significantly improve the existing ones whose unsatisfactory performances have been widely recognized. The success of the project will reduce the high cost for experiments and speed up the process of drug discovery. The natural collaborations among mathematics, biosciences, and pharmaceutical industry in the proposed research make it convenient to transform the mathematical research into the life-saving reality. This highly interdisciplinary project brings exciting opportunities for students and postdoctoral researchers to receive training in mathematical bioscientific research and to gain experience of working in biomedical industry. The project also provides material for an urgently needed course on mathematical and computational molecular biology.