Long-time conformational transitions of alanine dipeptide in aqueous solution: Continuous and discrete-state kinetic models
Long-time conformational transitions of alanine dipeptide in aqueous solution: Continuous and discrete-state kinetic models
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DOI：
10.1021/jp048540w
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发表时间：
2004-12-16
影响因子：
3.3
通讯作者：
Levy, RM
中科院分区：
文献类型：
--
作者：
Chekmarev, DS;Ishida, T;Levy, RM
我们提出了一个溶剂化的丙氨酸二肽分子的热力学，构象动力学和动力学分析。溶剂化处理的OPLS/分析广义出生与非极性相互作用的有效势模型的框架。利用加权直方图分析方法，在一系列多窗口伞形采样全原子模拟中生成了有效自由能图。一个布朗动力学方法被用来研究室温下的二肽动力学。为了模拟现实的动态的丙氨酸二肽在水中的构象相互转化，控制的简化模型的时间演变的参数被选择来模拟显式地处理溶质和溶剂的模型的中间时间动态。发现“快”C7（eq）-> alpha（R）跃迁的特征时间（平均首次通过时间）约为249 ps，与先前报道的研究结果非常一致。从微秒布朗动力学轨迹的系综中，我们能够以高统计精度数值估计“慢”跃迁α（R）-> C7（ax）的平均跃迁时间，发现其约为11 us。通过引入由四种状态（α（R）、β/C5/C7（eq）、α（L）和C7（ax））和12个速率常数组成的离散状态动力学模型来进一步分析二肽的构象动力学，该模型再现了布朗动力学模拟的长时间行为。这里描述的模拟补充和帮助激励单分子光谱研究丙氨酸二肽和其他肽在水溶液中。连续动力学和离散状态动力学模型之间建立的密切对应关系为使用详细的全原子有效势研究较大多肽的长时间动力学行为提供了可能的途径。
We present an analysis of the thermodynamics, conformational dynamics, and kinetics of the solvated alanine dipeptide molecule. Solvation was treated in the framework of the OPLS/analytic generalized born with nonpolar interactions effective potential model. The effective free energy map was generated in a series of multiwindow umbrella sampling all-atom simulations using the weighted histogram analysis method. A Brownian dynamics approach was used to examine the room-temperature dynamics of the dipeptide. To emulate the realistic dynamics of conformational interconversions of the alanine dipeptide in water, the parameters that govern the time evolution of the reduced model were chosen to mimic the intermediate-time dynamics of a model which treats both the solute and the solvent explicitly. The characteristic time (mean first passage time) for the "fast" C7(eq) --> alpha(R) transition was found to be around 249 ps in good agreement with the results of previously reported studies. From an ensemble of microsecond Brownian dynamics trajectories we were able to numerically estimate with high statistical precision the mean transition time for the "slow" transition alpha(R) --> C7(ax), which was found to be approximately I I us. Conformational kinetics of the dipeptide was further analyzed by introducing a discrete-state kinetic model consisting of four states (alpha(R), beta/C5/C7(eq), alpha(L), and C7(ax)) and 12 rate constants, which reproduces the long-time behavior of the Brownian dynamics simulations. The simulations described here complement and help to motivate single-molecule spectroscopic studies of alanine dipeptide and other peptides in aqueous solution. The close correspondence established between the continuous dynamics and a discrete-state kinetic model provides a possible route for studying the long-time kinetic behavior of larger polypeptides using detailed all-atom effective potentials.