Global Minimization of Nonconvex Energy Functions: Molecular Conformation and Protein Folding

本研究的目的是研究计算一类非凸能量函数的全局极小值的算法的设计、分析和实现。分子生物物理和生物化学中最重要和最具挑战性的问题之一是计算给定氨基酸序列的球状蛋白质的天然三维构象(折叠状态)，可能是在附加试剂(例如药物)存在的情况下。势能函数的最小化在确定某些分子簇和蛋白质的基态或稳定态时起着重要作用。因为，在几乎所有的情况下，势能函数都是非凸的，因此得到了；主要的障碍是缺乏足够的全局最小化方法来解决这些高维问题。我们的研究将集中在：(A)确定能够可靠地模拟蛋白质行为的合适的能量函数，以及(B)能够在给定蛋白质结构的许多自由度的情况下找到非凸能量函数的全局极小值的全局优化方法。

The objective of the proposed research is the study of the design, analysis, and implementation of algorithms for computing the global minima of a class of nonconvex energy functions. One of the most significant and challenging problems in molecular biophysics and biochemistry is that of computing the native 3-dimensional conformation (folded state) of a globular protein given its amino acid sequence, possibly in the presence of additional agents (e.g. drugs). The minimization of potential energy functions plays an important role in the determination of ground states or stable states of certain classes of molecular clusters and proteins. Since, in almost all the cases, the potential energy function is nonconvex and therefore has been made; the primary impediment is the lack of adequate global minimization methods for these large-dimensionality problems. Our research will focus on: (a) determination of suitable energy functions that can reliably model protein behaviour and (b) global optimization methods that can find global minima of nonconvex energy functions given the many degrees of freedom available to protein structures.