HIV-1 protease function and structure studies with the simplicial neighborhood analysis of protein packing method.
HIV-1 protease function and structure studies with the simplicial neighborhood analysis of protein packing method.
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DOI：
10.1002/prot.22094
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发表时间：
2008-11-15
影响因子：
2.9
通讯作者：
Tropsha, Alexander
中科院分区：
文献类型：
--
作者：
Zhang, Shuxing;Kaplan, Andrew H.;Tropsha, Alexander
关键词：
采用蛋白质包装的简单邻域分析（SNAPP）方法预测突变对HIV-1蛋白酶（HIVP）酶活性的影响。SNAPP依赖于一个四体统计评分函数，该函数来源于对来自蛋白质数据库的蛋白质结构的多样性和代表性子集中的空间最近邻残基组成偏好的分析。该方法被应用于分析HIVP突变体中的疏水核心以及在两个蛋白酶单体之间的界面处的残基取代。在计算中采用野生型和栓系结构两者。我们获得了ΔSNAPP评分（即，野生型和突变蛋白之间SNAPP得分的差异）和蛋白酶对系链结构的催化活性。一个较弱的，但显着的相关性也得到了非栓系结构。我们的分析确定了在疏水核心和二聚体界面（DI），这是非常重要的蛋白酶功能的残基。这项研究表明，SNAPP方法的诱变研究和蛋白质工程的合理设计的潜在效用。
The Simplicial Neighborhood Analysis of Protein Packing (SNAPP) method was used to predict the effect of mutagenesis on the enzymatic activity of the HIV-1 protease (HIVP). SNAPP relies on a four-body statistical scoring function derived from the analysis of spatially nearest neighbor residue compositional preferences in a diverse and representative subset of protein structures from the Protein Data Bank. The method was applied to the analysis of HIVP mutants with residue substitutions in the hydrophobic core as well as at the interface between the two protease monomers. Both wild type and tethered structures were employed in the calculations. We obtained a strong correlation, with R2 as high as 0.96, between ΔSNAPP score (i.e., the difference in SNAPP scores between wild type and mutant proteins) and the protease catalytic activity for tethered structures. A weaker but significant correlation was also obtained for non-tethered structures as well. Our analysis identified residues both in the hydrophobic core and at the dimeric interface (DI) that are very important for the protease function. This study demonstrates a potential utility of the SNAPP method for rational design of mutagenesis studies and protein engineering.
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影响因子：
8
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Hong, L;Zhang, XJC;Tang, J
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影响因子：
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通讯作者：
YOSHINAKA, Y
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作者：
Briggs, JAG;Gruenewald, K;Fuller, SD
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Fuller, SD