A generalized Langevin dynamics approach to model solvent dynamics effects on proteins via a solvent-accessible surface. The carboxypeptidase A inhibitor protein as a model
A generalized Langevin dynamics approach to model solvent dynamics effects on proteins via a solvent-accessible surface. The carboxypeptidase A inhibitor protein as a model
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一种广义朗之万动力学方法，通过溶剂可及的表面来模拟溶剂动力学对蛋白质的影响。
DOI：
10.1007/s002140000183
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发表时间：
2000
影响因子：
1.7
通讯作者：
O. Tapia
中科院分区：
文献类型：
--
作者：
B. Oliva;X. Daura;E. Querol;F. Avilés;O. Tapia
抽象。广义朗之万动力学（GLD）计划推导出（生物）大分子具有内部结构，任意形状和尺寸大于溶剂分子（即蛋白质）。溶剂可及表面积（SASA）的概念用于通过外力将溶剂效应纳入，从而避免其明确的分子表示。在GROMOS分子动力学（MD）程序中实现了模拟算法，包括随机力和记忆效应，而溶剂化效应通过表面积的导数进入。马铃薯羧肽酶抑制剂（PCI），一种小的蛋白质，是用来数值测试的方法。该分子具有N-和C-末端尾部，其结构和波动依赖于溶剂。深入分析了1 ns的MD轨迹。X射线和NMR结构与MD模拟结合使用，有和没有明确的溶剂，以衡量结果的质量。所有的分析表明，GLD模拟接近的MD模拟与明确的简单点电荷模型的水分子所获得的结果。极性原子的SASA显示出朝向溶剂方向的自然暴露。完成FLS溶剂模拟以感测记忆效应。这里提出的方法和结果可能是非常有价值的开发替代使用明确的溶剂分子在分子动力学模拟蛋白质，扩大其使用和探索的时间尺度。
Abstract. A generalized Langevin dynamics (GLD) scheme is derived for (bio)macromolecules having internal structure, arbitrary shapes and a size larger than solvent molecules (i.e. proteins). The concept of solvent-accessible surface area (SASA) is used to incorporate solvent effects via external forces thereby avoiding its explicit molecular representation. A simulation algorithm is implemented in the GROMOS molecular dynamics (MD) program including random forces and memory effects, while solvation effects enter via derivatives of the surface area. The potato carboxypeptidase inhibitor (PCI), a small protein, is used to numerically test the approach. This molecule has N- and C-terminal tails whose structure and fluctuations are solvent dependent. A 1-ns MD trajectory was analyzed in depth. X-ray and NMR structures are used in conjunction with MD simulations with and without explicit solvent to gauge the quality of the results. All the analyses showed that the GLD simulation approached the results obtained for the MD simulation with explicit simple-point-charge-model water molecules. The SASAs of the polar atoms show a natural exposure towards the solvent direction. A FLS solvent simulation was completed in order to sense memory effects. The approach and results presented here could be of great value for developing alternatives to the use of explicit solvent molecules in the MD simulation of proteins, expanding its use and the time-scale explored.