Monticelli Luca, Sorin Eric J, Tieleman D Peter, Pande Vijay S, Colombo Giorgio
Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
J Comput Chem. 2008 Aug;29(11):1740-52. doi: 10.1002/jcc.20935.
Molecular dynamics simulations of the RN24 peptide, which includes a diverse set of structurally heterogeneous states, are carried out in explicit solvent. Two approaches are employed and compared directly under identical simulation conditions. Specifically, we examine sampling by two individual long trajectories (microsecond timescale) and many shorter (MS) uncoupled trajectories. Statistical analysis of the structural properties indicates a qualitative agreement between these approaches. Microsecond timescale sampling gives large uncertainties on most structural metrics, while the shorter timescale of MS simulations results in slight structural memory for beta-structure starting states. Additionally, MS sampling detects numerous transitions on a relatively short timescale that are not observed in microsecond sampling, while long simulations allow for detection of a few transitions on significantly longer timescales. A correlation between the complex free energy landscape and the kinetics of the equilibrium is highlighted by principal component analysis on both simulation sets. This report highlights the increased precision of the MS approach when studying the kinetics of complex conformational change, while revealing the complementary insight and qualitative agreement offered by far fewer individual simulations on significantly longer timescales.
对包含多种结构异质状态的RN24肽进行了分子动力学模拟，模拟在显式溶剂中进行。采用了两种方法，并在相同的模拟条件下直接进行比较。具体而言，我们通过两条单独的长轨迹（微秒时间尺度）和许多较短的（毫秒）非耦合轨迹来检验采样情况。对结构特性的统计分析表明这些方法之间存在定性的一致性。微秒时间尺度的采样在大多数结构指标上给出了较大的不确定性，而毫秒模拟的较短时间尺度导致对β结构起始状态有轻微的结构记忆。此外，毫秒采样在相对较短的时间尺度上检测到许多在微秒采样中未观察到的转变，而长时间模拟则允许在长得多的时间尺度上检测到一些转变。对两个模拟集进行主成分分析突出了复杂自由能景观与平衡动力学之间的相关性。本报告强调了在研究复杂构象变化动力学时毫秒方法的更高精度，同时揭示了在长得多的时间尺度上进行少得多的单个模拟所提供的互补见解和定性一致性。
