Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone φ, ψ and side-chain χ(1) and χ(2) dihedral angles.
Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone φ, ψ and side-chain χ(1) and χ(2) dihedral angles.
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DOI：
10.1021/ct300400x
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发表时间：
2012-09-11
影响因子：
5.5
通讯作者：
MacKerell, Alexander D., Jr.
中科院分区：
文献类型：
--
作者：
Best, Robert B.;Zhu, Xiao;Shim, Jihyun;Lopes, Pedro E. M.;Mittal, Jeetain;Feig, Michael;MacKerell, Alexander D., Jr.
虽然目前的CHARMM22/CMAP蛋白质加性力场的质量已经在大量应用中得到证明，但已经注意到该模型在折叠模拟中螺旋和扩展构象采样之间的平衡方面的局限性。为了克服这一点，以及在模型中进行其他改进，我们提出了一种改进的组合，这种组合应该会提高蛋白质模拟的准确性。针对弱结构多肽的实验溶液核磁共振数据，对共同（非Gly， Pro）主链CMAP电位进行了修正，导致α-螺旋和Ramachandran图扩展区域的能量重新平衡，纠正了CHARMM22/CMAP的α-螺旋偏差。Gly和Pro cmap已经改装成更精确的量子力学能量表面。通过拟合骨架相关的量子力学能面来优化侧链扭转参数，然后针对未折叠蛋白质的NMR标量偶联进行额外的经验优化。然后针对未用于指导参数化的数据对修订后的力场进行了全面验证：(i)比较了八种蛋白质在其晶体环境中的晶体结构模拟；（ii）与弱结构肽骨架标量偶联的比较；（iii）比较折叠蛋白中主链和侧链的核磁共振残余偶极偶联和标量偶联；（iv）微型蛋白的平衡折叠。结果表明，修订后的CHARMM 36参数代表了蛋白质建模和模拟研究的改进模型，包括蛋白质折叠、组装和功能相关构象变化的研究。
While the quality of the current CHARMM22/CMAP additive force field for proteins has been demonstrated in a large number of applications, limitations in the model with respect to the equilibrium between the sampling of helical and extended conformations in folding simulations have been noted. To overcome this, as well as make other improvements in the model, we present a combination of refinements that should result in enhanced accuracy in simulations of proteins. The common (non Gly, Pro) backbone CMAP potential has been refined against experimental solution NMR data for weakly structured peptides, resulting in a rebalancing of the energies of the α-helix and extended regions of the Ramachandran map, correcting the α-helical bias of CHARMM22/CMAP. The Gly and Pro CMAPs have been refitted to more accurate quantum-mechanical energy surfaces. Side-chain torsion parameters have been optimized by fitting to backbone-dependent quantum-mechanical energy surfaces, followed by additional empirical optimization targeting NMR scalar couplings for unfolded proteins. A comprehensive validation of the revised force field was then performed against data not used to guide parametrization: (i) comparison of simulations of eight proteins in their crystal environments with crystal structures; (ii) comparison with backbone scalar couplings for weakly structured peptides; (iii) comparison with NMR residual dipolar couplings and scalar couplings for both backbone and side-chains in folded proteins; (iv) equilibrium folding of mini-proteins. The results indicate that the revised CHARMM 36 parameters represent an improved model for the modeling and simulation studies of proteins, including studies of protein folding, assembly and functionally relevant conformational changes.
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影响因子：
2.9
作者：
Best, Robert B.;Mittal, Jeetain
通讯作者：
Mittal, Jeetain
影响因子：
7.3
作者：
Bernard, Denzil;Coop, Andrew;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.
影响因子：
15
作者：
Chou, JJ;Case, DA;Bax, A
通讯作者：
Bax, A
影响因子：
3.4
作者：
Best, Robert B.;Buchete, Nicolae-Viorel;Hummer, Gerhard
通讯作者：
Hummer, Gerhard
影响因子：
3.3
作者：
Aliev, Abil E.;Courtier-Murias, Denis
通讯作者：
Courtier-Murias, Denis