Fluctuation Relations to Calculate Protein Redox Potentials from Molecular Dynamics Simulations.
Fluctuation Relations to Calculate Protein Redox Potentials from Molecular Dynamics Simulations.
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DOI：
10.1021/acs.jctc.3c00785
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发表时间：
2024-01-09
影响因子：
5.5
通讯作者：
Mulholland, A. J.
中科院分区：
文献类型：
--
作者：
Oliveira, A. S. F.;Rubio, J.;Noble, C. E. M.;Anderson, J. L. R.;Anders, J.;Mulholland, A. J.
蛋白质氧化还原电位的可调设计有望在生物技术和催化领域开辟一系列应用。本文介绍了一种结合涨落关系和分子动力学模拟计算氧化还原电位变化的方法。它包括还原态和氧化态的模拟，然后是它们之间的瞬时转换。利用Kubo-Onsager方法获得了扰动引入的能量差。利用详细的波动关系与贝叶斯推理相结合，这些数据被有效地后处理为氧化还原电位的估计。这种新方法被称为MD + CB，在一个全新的四螺旋束血红素蛋白（m4D2“maquette”）和五个设计的突变体上进行了测试，其中包括本工作中实验表征的一些突变体。发现MD + CB方法执行可靠，给出的氧化还原电位位移与突变体的实验值具有相当好的相关性（0.85）。MD + CB方法也与使用连续静电方法的氧化还原电位位移预测相比较。MD + CB方法中采用的估计方法可直接转移到标准平衡MD模拟中，并有望用于氧化还原蛋白工程和设计应用。
The tunable design of protein redox potentials promises to open a range of applications in biotechnology and catalysis. Here, we introduce a method to calculate redox potential changes by combining fluctuation relations with molecular dynamics simulations. It involves the simulation of reduced and oxidized states, followed by the instantaneous conversion between them. Energy differences introduced by the perturbations are obtained using the Kubo-Onsager approach. Using a detailed fluctuation relation coupled with Bayesian inference, these are postprocessed into estimates for the redox potentials in an efficient manner. This new method, denoted MD + CB, is tested on a de novo four-helix bundle heme protein (the m4D2 “maquette”) and five designed mutants, including some mutants characterized experimentally in this work. The MD + CB approach is found to perform reliably, giving redox potential shifts with reasonably good correlation (0.85) to the experimental values for the mutants. The MD + CB approach also compares well with redox potential shift predictions using a continuum electrostatic method. The estimation method employed within the MD + CB approach is straightforwardly transferable to standard equilibrium MD simulations and holds promise for redox protein engineering and design applications.
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影响因子：
4.1
作者：
BENNETT, CH
通讯作者：
BENNETT, CH
影响因子：
2.9
作者：
BASHFORD, D;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
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作者：
Crooks, GE
通讯作者：
Crooks, GE
影响因子：
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作者：
BERENDSEN, HJC;VANDERSPOEL, D;VANDRUNEN, R
通讯作者：
VANDRUNEN, R
影响因子：
4.3
作者：
Ayuso-Fernandez, Ivan;De Lacey, Antonio L.;Martinez, Angel T.
通讯作者：
Martinez, Angel T.