One-dimensional free-energy profiles of complex systems: Progress variables that preserve the barriers
One-dimensional free-energy profiles of complex systems: Progress variables that preserve the barriers
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DOI：
10.1021/jp060039b
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发表时间：
2006-06-29
影响因子：
3.3
通讯作者：
Karplus, Martin
中科院分区：
文献类型：
--
作者：
Krivov, Sergei V.;Karplus, Martin
我们表明，平衡的最小切割过程中引入的PNAS 2004年，101，14766可以被重新解释为一种方法，用于解决约束优化问题，找到最小切割之间的削减与一个特定的值的附加功能的节点上的任何一方的削减。这种加性函数（例如，反应物区域的配分函数）可以用作进程坐标以确定蛋白质折叠反应以及其它复杂反应的自由能表面的一维轮廓（FEP）。该算法是基于网络（从平衡分子动力学模拟获得），代表计算的反应行为。得到的FEP给出了作为进度坐标的函数的自由能的精确值;即，在进度坐标的每个值处，从具有最小配分函数的表面获得轮廓，这些表面将完整自由能表面划分在两个选定的端点之间。在许多情况下，平衡最小割方法只给出有限的一组点的结果。示出了基于p（折叠）的近似方法，以提供进度坐标的更完整的值集的轮廓。模型问题和现实系统（β-发夹蛋白G，LJ（38）集群）的方法的应用。
We show that the balanced minimum-cut procedure introduced in PNAS 2004, 101, 14766 can be reinterpreted as a method for solving the constrained optimization problem of finding the minimum cut among the cuts with a particular value of an additive function of the nodes on either side of the cut. Such an additive function (e.g., the partition function of the reactant region) can be used as a progress coordinate to determine a one-dimensional profile (FEP) of the free-energy surface of the protein-folding reaction as well as other complex reactions. The algorithm is based on the network (obtained from an equilibrium molecular dynamics simulation) that represents the calculated reaction behavior. The resulting FEP gives the exact values of the free energy as a function of the progress coordinate; i.e., at each value of the progress coordinate, the profile is obtained from the surface with the minimal partition function among the surfaces that divide the full free-energy surface between two chosen end points. In many cases, the balanced minimum-cut procedure gives results for only a limited set of points. An approximate method based on p(fold) is shown to provide the profile for a more complete set of values of the progress coordinate. Applications of the approach to model problems and to realistic systems (beta-hairpin of protein G, LJ(38) cluster) are presented.