Peptide backbone sampling convergence with the adaptive biasing force algorithm.
Peptide backbone sampling convergence with the adaptive biasing force algorithm.
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DOI：
10.1021/jp309741j
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发表时间：
2013-01-17
影响因子：
3.3
通讯作者：
Guvench, Olgun
中科院分区：
文献类型：
--
作者：
Faller, Christina E.;Reilly, Kyle A.;Hills, Ronald D., Jr.;Guvench, Olgun
生物分子系统中反应坐标的完整玻尔兹曼采样仍然是无偏分子动力学模拟的一个挑战。越来越多的方法已经开发应用偏差生物分子系统，以加强采样，同时使状态的无偏（玻尔兹曼）分布的恢复。自适应偏置力（ABF）算法就是这样的一种方法，它的工作原理是利用模拟过程中逐渐积累的力的估计值来抵消沿期望的反应坐标的平均力。在模拟完成后，通过对平均力进行积分得到平均力的势，从而得到状态的玻尔兹曼分布。为了描述蛋白质环采样等应用中的预期性能，利用全原子显式水分子动力学模拟，将ABF应用于20种氨基酸二肽的Ramachandran φ /ψ骨架二面体反应坐标的全范围。在三次50-ns模拟中，大约一半的二肽表现出平均力势作为φ /ψ的函数的鲁棒和快速收敛，而其余的二肽表现出不同程度的不完全收敛。实现收敛ABF采样的最大困难是在支链氨基酸苏氨酸和缬氨酸中，以及脯氨酸的特殊情况下。在无偏对照分子动力学模拟中未观察到的反式到顺式肽键异构化使脯氨酸二肽取样进一步复杂化。总的来说，ABF方法被发现是采样整个φ /ψ的20个氨基酸的反应坐标的稳健手段，包括在标准分子动力学模拟中通常无法获得的高自由能区。
Complete Boltzmann sampling of reaction coordinates in biomolecular systems continues to be a challenge for unbiased molecular dynamics simulations. A growing number of methods have been developed for applying biases to biomolecular systems to enhance sampling while enabling recovery of the unbiased (Boltzmann) distribution of states. The Adaptive Biasing Force (ABF) algorithm is one such method, and works by canceling out the average force along the desired reaction coordinate(s) using an estimate of this force progressively accumulated during the simulation. Upon completion of the simulation, the potential of mean force, and therefore Boltzmann distribution of states, is obtained by integrating this average force. In an effort to characterize the expected performance in applications such as protein loop sampling, ABF was applied to the full ranges of the Ramachandran ϕ/ψ backbone dihedral reaction coordinates for dipeptides of the 20 amino acids using all-atom explicit-water molecular dynamics simulations. Approximately half of the dipeptides exhibited robust and rapid convergence of the potential of mean force as a function of ϕ/ψ in triplicate 50-ns simulations, while the remainder exhibited varying degrees of less complete convergence. The greatest difficulties in achieving converged ABF sampling were seen in the branched-sidechain amino acids threonine and valine, as well as the special case of proline. Proline dipeptide sampling was further complicated by trans-to-cis peptide bond isomerization not observed in unbiased control molecular dynamics simulations. Overall, the ABF method was found to be a robust means of sampling the entire ϕ/ψ reaction coordinate for the 20 amino acids, including high free-energy regions typically inaccessible in standard molecular dynamics simulations.
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