Additive CHARMM36 Force Field for Nonstandard Amino Acids.
Additive CHARMM36 Force Field for Nonstandard Amino Acids.
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DOI：
10.1021/acs.jctc.1c00254
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发表时间：
2021-06-08
影响因子：
5.5
通讯作者：
Aleksandrov A
中科院分区：
文献类型：
--
作者：
Croitoru A;Park SJ;Kumar A;Lee J;Im W;MacKerell AD Jr;Aleksandrov A
非标准氨基酸在自然界中丰富，它们在各种细胞过程中发挥关键作用，并且可以在实验室中合成，例如用于制造一系列药物。在这项工作中，我们将加性全原子CHARMM 36和CHARMM一般力场（CGenFF）扩展到了333个非标准氨基酸的大集合。这些包括具有非标准侧链的氨基酸，例如翻译后修饰的和人工的氨基酸，以及具有修饰的骨架基团的氨基酸，例如由几种氨基酸组成的发色团。代表非标准氨基酸的模型化合物被参数化为质子化状态，可能在生理pH值为7，对于一些更常见的残基，在D-和L-立体异构体。考虑到所有的质子化，互变异构和立体异构形式，共406个非标准氨基酸参数化。重点放在分子内和分子间参数的质量。部分电荷来自模型化合物的偶极矩，静电势，和与水的相互作用的量子力学（QM）数据。优化的所有分子内参数，包括扭转角参数，进行对QM绝热势能面（PES）扫描的信息。特别强调的是把质量的条款相应的PES周围旋转二面角。力场的验证是基于20个蛋白质复合物含有不同的非标准氨基酸的分子动力学模拟。总体而言，所提出的参数将允许计算研究的蛋白质含有非标准氨基酸，包括天然和人工残基的范围广泛。
Nonstandard amino acids are both abundant in nature, where they play a key role in various cellular processes, and can be synthesized in laboratories, for example, for the manufacture of a range of pharmaceutical agents. In this work we have extended the additive all-atom CHARMM36 and CHARMM General force field (CGenFF) to a large set of 333 nonstandard amino acids. These include both amino acids with nonstandard side chains, such as post translationally modified and artificial amino acids as well as amino acids with modified backbone groups, such as chromophores composed of several amino acids. Model compounds representative of the nonstandard amino acids were parametrized for protonation states that are likely at the physiological pH of 7 and, for some more common residues, in both D- and L-stereoisomers. Considering all protonation, tautomeric, and stereoisomeric forms, a total of 406 nonstandard amino acids were parametrized. Emphasis was placed on the quality of both intra- and intermolecular parameters. Partial charges were derived using quantum mechanical (QM) data on model compound dipole moments, electrostatic potentials, and interactions with water. Optimization of all intramolecular parameters, including torsion angle parameters, was performed against information from QM adiabatic potential energy surface (PES) scans. Special emphasis was put on the quality of terms corresponding to PES around rotatable dihedral angles. Validation of the force field was based on molecular dynamics simulations of 20 protein complexes containing different nonstandard amino acids. Overall, the presented parameters will allow for computational studies of a wide range of proteins containing nonstandard amino acids, including natural and artificial residues.
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影响因子：
2.9
作者：
French, Jarrod B.;Cen, Yana;Vrablik, Tracy L.;Xu, Ping;Allen, Eleanor;Hanna-Rose, Wendy;Sauve, Anthony A.
通讯作者：
Sauve, Anthony A.
影响因子：
2.9
作者：
Barondeau, DP;Kassmann, CJ;Getzoff, ED
通讯作者：
Getzoff, ED
影响因子：
3
作者：
Gfeller, David;Michielin, Olivier;Zoete, Vincent
通讯作者：
Zoete, Vincent
影响因子：
15
作者：
Aleksandrov, Alexey;Simonson, Thomas
通讯作者：
Simonson, Thomas
影响因子：
5.5
作者：
Best, Robert B.;Zhu, Xiao;Shim, Jihyun;Lopes, Pedro E. M.;Mittal, Jeetain;Feig, Michael;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.