A fast loop-closure algorithm to accelerate residue matching in computational enzyme design
A fast loop-closure algorithm to accelerate residue matching in computational enzyme design
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DOI：
10.1007/s00894-016-2915-2
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发表时间：
2016-01
影响因子：
2.2
通讯作者：
Jing Xue;Xiaoqiang Huang;Min Lin;Yushan Zhu
中科院分区：
文献类型：
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作者：
Jing Xue;Xiaoqiang Huang;Min Lin;Yushan Zhu
在惰性支架上构建活性部位在化学生物学中仍然是一个挑战。在这里，我们描述了一个基于牛顿方向的催化残基匹配的快速闭合环算法在我们的酶设计程序ProdaMatch中的结合。这是为了高精度地确定催化残基的位置和几何构型以及过渡态的位置，以满足催化残基与过渡态相互作用的几何约束而开发的。对来自测试集中21个循环的64,827个初始循环的闭合结果表明，99.51%的初始循环在不到400个迭代步骤内闭合到0.05%以内，而绝大多数初始循环在100个迭代步骤内闭合。ProdaMatch的修订版包含新的循环闭合算法，在本机活性位点重复测试中识别了10个支架的所有本机匹配。当将催化残基与支架匹配时，其快速和准确使此版本的ProdaMatch通过结合更复杂的理论酶模型来潜在地用于支架选择，这些模型可能在从头开始的酶设计中产生更高的初始活性。
Constructing an active site on an inert scaffold is still a challenge in chemical biology. Herein, we describe the incorporation of a Newton-direction-based fast loop-closure algorithm for catalytic residue matching into our enzyme design program ProdaMatch. This was developed to determine the sites and geometries of the catalytic residues as well as the position of the transition state with high accuracy in order to satisfy the geometric constraints on the interactions between catalytic residues and the transition state. Loop-closure results for 64,827 initial loops derived from 21 loops in the test set showed that 99.51 % of the initial loops closed to within 0.05 Å in fewer than 400 iteration steps, while the large majority of the initial loops closed within 100 iteration steps. The revised version of ProdaMatch containing the novel loop-closure algorithm identified all native matches for ten scaffolds in the native active-site recapitulation test. Its high speed and accuracy when matching catalytic residues with a scaffold make this version of ProdaMatch potentially useful for scaffold selection through the incorporation of more complex theoretical enzyme models which may yield higher initial activities in de novo enzyme design.