Empirical Optimization of Interactions between Proteins and Chemical Denaturants in Molecular Simulations.
Empirical Optimization of Interactions between Proteins and Chemical Denaturants in Molecular Simulations.
复制标题
分子模拟中蛋白质与化学变性剂之间相互作用的实证优化。
DOI：
10.1021/acs.jctc.5b00778
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发表时间：
2015
影响因子：
5.5
通讯作者：
Best,RobertB
中科院分区：
文献类型：
--
作者：
Zheng,Wenwei;Borgia,Alessandro;Borgia,MadeleineB;Schuler,Benjamin;Best,RobertB
化学变性剂是最常用的扰动，用于研究蛋白质稳定性和折叠动力学以及未折叠多肽的特性。我们以最近平衡蛋白质和水相互作用的工作以及尿素和氯化胍溶液性质的精确模型为基础，开发了一种能够捕获蛋白质和变性剂之间相互作用强度的组合力场。我们使用每种变性剂中四甘氨酸肽模型的溶解度数据，通过新颖的模拟方法来调整蛋白质与变性剂的相互作用。我们根据更复杂序列的数据验证结果：球状蛋白 CspTman 的 34 个残基片段的单分子 Förster 共振能量转移数据、变性剂溶液中无序肽 C(AGQ)nW 的光诱导电子转移猝灭数据以及微型蛋白 Trp 笼的化学变性。组合力场模型应该有助于我们理解变性机制和解释实验。
Chemical denaturants are the most commonly used perturbation applied to study protein stability and folding kinetics as well as the properties of unfolded polypeptides. We build on recent work balancing the interactions of proteins and water, and accurate models for the solution properties of urea and guanidinium chloride, to develop a combined force field that is able to capture the strength of interactions between proteins and denaturants. We use solubility data for a model tetraglycine peptide in each denaturant to tune the protein–denaturant interaction by a novel simulation methodology. We validate the results against data for more complex sequences: single-molecule Förster resonance energy transfer data for a 34-residue fragment of the globular protein CspTmand photoinduced electron transfer quenching data for the disordered peptides C(AGQ)nW in denaturant solution as well as the chemical denaturation of the mini-protein Trp cage. The combined force field model should aid our understanding of denaturation mechanisms and the interpretation of experiment.