Genfold: A genetic algorithm for folding protein structures using NMR restraints
Genfold: A genetic algorithm for folding protein structures using NMR restraints
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Genfold：使用 NMR 约束折叠蛋白质结构的遗传算法
DOI：
10.1002/pro.5560070230
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发表时间：
1998
期刊：
影响因子：
8
通讯作者：
Michael P. Williamson
中科院分区：
文献类型：
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作者：
M. J. Bayley;Gareth Jones;P. Willett;Michael P. Williamson
我们报告的开发和验证的程序GENFOLD，遗传算法，计算蛋白质的结构，从NMR获得的限制，如来自核Overhauser效应的距离，二面角来自耦合常数。该程序已经在三种蛋白质上进行了测试：POU结构域（一种小的三螺旋DNA结合蛋白），牛胰蛋白酶抑制剂（BPTI）和尼日尔曲霉葡糖淀粉酶I的淀粉结合结构域，一种108残基的β折叠蛋白。使用公开的NMR限制计算每种蛋白质的结构。此外，使用由高分辨率晶体结构生成的人工约束计算BPTI的结构。在所有情况下，最适合的计算结构接近目标结构，并且可以通过低温模拟退火细化来细化到与目标结构无法区分的结构。该程序的有效性类似于距离几何和模拟退火方法，并且能够使用非常广泛的约束作为输入。因此，它可以很容易地扩展到大蛋白质的结构的计算，其中几个NOE限制可能是可用的。
We report the development and validation of the program GENFOLD, a genetic algorithm that calculates protein structures using restraints obtained from NMR, such as distances derived from nuclear Overhauser effects, and dihedral angles derived from coupling constants. The program has been tested on three proteins: the POU domain (a small three‐helix DNA‐binding protein), bovine pancreatic trypsin inhibitor (BPTI), and the starch‐binding domain from Aspergillus niger glucoamylase I, a 108‐residue β‐sheet protein. Structures were calculated for each protein using published NMR restraints. In addition, structures were calculated for BPTI using artificial restraints generated from a high‐resolution crystal structure. In all cases the fittest calculated structures were close to the target structure, and could be refined to structures indistinguishable from the target structures by means of a low‐temperature simulated annealing refinement. The effectiveness of the program is similar to that of distance geometry and simulated annealing methods, and it is capable of using a very wide range of restraints as input. It can thus be readily extended to the calculation of structures of large proteins, for which few NOE restraints may be available.