ATP-Magnesium Coordination: Protein Structure-Based Force Field Evaluation and Corrections.
ATP-Magnesium Coordination: Protein Structure-Based Force Field Evaluation and Corrections.
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DOI：
10.1021/acs.jctc.0c01205
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发表时间：
2021-03-09
影响因子：
5.5
通讯作者：
Grubmüller H
中科院分区：
文献类型：
--
作者：
Buelens FP;Leonov H;de Groot BL;Grubmüller H
在涉及三磷酸腺苷（ATP）的众多生物化学分子识别和催化过程中，常见的生物活性形式是其镁螯合物ATP·Mg 2+。在水溶液中，两个螯合几何形状占主导地位，区分由二齿和三齿镁2 +-磷酸盐协调。它们近似等能，但被高能量势垒隔开。基于力场的原子模拟研究，这种复杂的需要一个准确的表示其结构和能量。本文重点研究了ATP·Mg ~（2+）配位的能量学。应用增强的采样方案，以规避协调模式之间的过渡，令人望而却步的缓慢采样，我们观察到琥珀色和CHARMM力场描述之间的矛盾，最突出的是在反对的预测的青睐协调模式。通过针对不同的ATP·Mg 2 +-蛋白质复合物结构进行进一步的构型自由能计算，以补充有限的实验数据，我们量化了每个力场的系统偏差。力场计算强烈预测实验观察到的协调模式，使添加剂校正的协调自由能，提供密切的协议与实验。我们重新评估了ATP·Mg 2+的力场描述在生物分子模拟中的适用性，并观察到，尽管CHARMM参数显示出对过度延伸的三磷酸盐构型的错误偏好，这将影响许多涉及ATP的常见生物分子模拟应用，力场能量图与实验测量的溶液几何形状和ATP·Mg ~（2+）的分布基本一致在蛋白质数据库中找到的结构。我们的力场评估和校正方法，最大限度地提高一致性的基础上，在PDB编码的结构信息的大型和异构的集合，应广泛适用于许多其他系统。
In the numerous molecular recognition and catalytic processes across biochemistry involving adenosine triphosphate (ATP), the common bioactive form is its magnesium chelate, ATP·Mg2+. In aqueous solution, two chelation geometries predominate, distinguished by bidentate and tridentate Mg2+–phosphate coordination. These are approximately isoenergetic but separated by a high energy barrier. Force field-based atomistic simulation studies of this complex require an accurate representation of its structure and energetics. Here we focused on the energetics of ATP·Mg2+ coordination. Applying an enhanced sampling scheme to circumvent prohibitively slow sampling of transitions between coordination modes, we observed striking contradictions between Amber and CHARMM force field descriptions, most prominently in opposing predictions of the favored coordination mode. Through further configurational free energy calculations, conducted against a diverse set of ATP·Mg2+–protein complex structures to supplement otherwise limited experimental data, we quantified systematic biases for each force field. The force field calculations were strongly predictive of experimentally observed coordination modes, enabling additive corrections to the coordination free energy that deliver close agreement with experiment. We reassessed the applicability of the thus corrected force field descriptions of ATP·Mg2+ for biomolecular simulation and observed that, while the CHARMM parameters display an erroneous preference for overextended triphosphate configurations that will affect many common biomolecular simulation applications involving ATP, the force field energy landscapes broadly agree with experimental measurements of solution geometry and the distribution of ATP·Mg2+ structures found in the Protein Data Bank. Our force field evaluation and correction approach, based on maximizing consistency with the large and heterogeneous collection of structural information encoded in the PDB, should be broadly applicable to many other systems.
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影响因子：
15
作者：
TAKEUCHI, H;MURATA, H;HARADA, I
通讯作者：
HARADA, I
影响因子：
3.7
作者：
Grant, Barry J.;Lukman, Suryani;Gorfe, Alemayehu A.
通讯作者：
Gorfe, Alemayehu A.
DOI：
10.33011/livecoms.2.1.18378
发表时间：
2020
期刊：
Living journal of computational molecular science
影响因子：
--
作者：
Mey AS;Allen BK;Macdonald HE;Chodera JD;Hahn DF;Kuhn M;Michel J;Mobley DL;Naden LN;Prasad S;Rizzi A;Scheen J;Shirts MR;Tresadern G;Xu H
通讯作者：
Xu H
影响因子：
3
作者：
Andreini, Claudia;Bertini, Ivano;Thornton, Janet M.
通讯作者：
Thornton, Janet M.
影响因子：
11.4
作者：
WALKER, JE;SARASTE, M;GAY, NJ
通讯作者：
GAY, NJ