Long time dynamics of Met-enkephalin: comparison of explicit and implicit solvent models.
Long time dynamics of Met-enkephalin: comparison of explicit and implicit solvent models.
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DOI：
10.1016/s0006-3495(02)75530-6
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发表时间：
2002-04
影响因子：
3.4
通讯作者：
Min-yi Shen My;K. Freed
中科院分区：
文献类型：
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作者：
Min-yi Shen My;K. Freed
脑啡肽是最小的阿片肽之一。但其动力学结构和受体对接机制尚不清楚。本文采用全原子分子动力学（MD）和含AMBER势函数的隐式水朗之万动力学（LD）模拟，以及水的三位点可转移分子间势（TIP3P）模型，研究了该神经元肽在液态水中的构象动力学。为了在物理时间上达到相同的模拟长度，完整的MD模拟需要的CPU时间是隐式水LD模拟的200倍。在隐式溶剂LD模拟中，溶剂的疏水性和介电行为是通过宏观溶剂化势、单一介电常数和原子摩擦系数来处理的，原子摩擦系数采用可达表面积法计算，TIP3P模型水粘度由纯TIP3P水的MD模拟确定。隐式溶剂动力学模拟得到的局部和全局动力学结果与显式溶剂动力学模拟的结果吻合得很好。模拟提供了与阿片肽dermorphin对δ受体的生物活性相关的构象限制的见解。
Met-enkephalin is one of the smallest opiate peptides. Yet, its dynamical structure and receptor docking mechanism are still not well understood. The conformational dynamics of this neuron peptide in liquid water are studied here by using all-atom molecular dynamics (MD) and implicit water Langevin dynamics (LD) simulations with AMBER potential functions and the three-site transferable intermolecular potential (TIP3P) model for water. To achieve the same simulation length in physical time, the full MD simulations require 200 times as much CPU time as the implicit water LD simulations. The solvent hydrophobicity and dielectric behavior are treated in the implicit solvent LD simulations by using a macroscopic solvation potential, a single dielectric constant, and atomic friction coefficients computed using the accessible surface area method with the TIP3P model water viscosity as determined here from MD simulations for pure TIP3P water. Both the local and the global dynamics obtained from the implicit solvent LD simulations agree very well with those from the explicit solvent MD simulations. The simulations provide insights into the conformational restrictions that are associated with the bioactivity of the opiate peptide dermorphin for theδ-receptor.