基于氨基酸残基贡献的蛋白质相互作用自由能模型:T4溶菌酶点突变稳定性的评估。

TECHNOLOGY Pub Date : 2019-03-01 Epub Date: 2019-04-26 DOI:10.1142/s233954781950002x
Lawrence J Williams, Brian J Schendt, Zachary R Fritz, Yonatan Attali, Robert H Lavroff, Martin L Yarmush
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引用次数: 1

摘要

在这里,我们提出了一个模型来估计给定蛋白质的每个氨基酸残基的相互作用自由能贡献。蛋白质相互作用能量以每个残基的相互作用因子μ来描述。通过由局部构象指数(σ)引导的氨基酸项(γ)的组合,多体相互作用隐含地以μ捕获。该模型能够构建给定折叠中蛋白质的相互作用因子热图,能够初步评估残基-残基相互作用的程度,并有助于对蛋白质结合特性进行定性和定量评估。该模型用于计算T4噬菌体溶菌酶突变体在七个位点上的热稳定性。对突变效应的定性评估提供了一个简单的理由,说明特定位点是否主要干扰天然或非天然状态,或两者兼而有之。所提出的模型与实验突变数据(R2=0.73)非常一致,并提出了一种将结构空间转换为能量空间的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A protein interaction free energy model based on amino acid residue contributions: Assessment of point mutation stability of T4 lysozyme.

A protein interaction free energy model based on amino acid residue contributions: Assessment of point mutation stability of T4 lysozyme.

A protein interaction free energy model based on amino acid residue contributions: Assessment of point mutation stability of T4 lysozyme.

A protein interaction free energy model based on amino acid residue contributions: Assessment of point mutation stability of T4 lysozyme.

Here we present a model to estimate the interaction free energy contribution of each amino acid residue of a given protein. Protein interaction energy is described in terms of per-residue interaction factors, μ. Multibody interactions are implicitly captured in μ through the combination of amino acid terms (γ) guided by local conformation indices (σ). The model enables construction of an interaction factor heat map for a protein in a given fold, allows prima facie assessment of the degree of residue-residue interaction, and facilitates a qualitative and quantitative evaluation of protein association properties. The model was used to compute thermal stability of T4 bacteriophage lysozyme mutants across seven sites. Qualitative assessment of mutational effects provides a straightforward rationale regarding whether a particular site primarily perturbs native or non-native states, or both. The presented model was found to be in good agreement with experimental mutational data (R 2 = 0.73) and suggests an approach by which to convert structure space into energy space.

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来源期刊
TECHNOLOGY
TECHNOLOGY ENGINEERING, MULTIDISCIPLINARY-
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