Wüstner Daniel, Sklenar Heinz
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M DK-5230, Denmark.
Theoretical Biophysics Group, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, Berlin D-13125, Germany.
Int J Mol Sci. 2014 Jan 24;15(2):1767-803. doi: 10.3390/ijms15021767.
Biological membranes are complex assemblies of many different molecules of which analysis demands a variety of experimental and computational approaches. In this article, we explain challenges and advantages of atomistic Monte Carlo (MC) simulation of lipid membranes. We provide an introduction into the various move sets that are implemented in current MC methods for efficient conformational sampling of lipids and other molecules. In the second part, we demonstrate for a concrete example, how an atomistic local-move set can be implemented for MC simulations of phospholipid monomers and bilayer patches. We use our recently devised chain breakage/closure (CBC) local move set in the bond-/torsion angle space with the constant-bond-length approximation (CBLA) for the phospholipid dipalmitoylphosphatidylcholine (DPPC). We demonstrate rapid conformational equilibration for a single DPPC molecule, as assessed by calculation of molecular energies and entropies. We also show transition from a crystalline-like to a fluid DPPC bilayer by the CBC local-move MC method, as indicated by the electron density profile, head group orientation, area per lipid, and whole-lipid displacements. We discuss the potential of local-move MC methods in combination with molecular dynamics simulations, for example, for studying multi-component lipid membranes containing cholesterol.
生物膜是由许多不同分子组成的复杂集合体,对其进行分析需要多种实验和计算方法。在本文中,我们解释了脂质膜原子蒙特卡罗(MC)模拟的挑战和优势。我们介绍了当前MC方法中为实现脂质和其他分子的高效构象采样而采用的各种移动集。在第二部分,我们通过一个具体例子展示了如何为磷脂单体和双层膜片的MC模拟实现原子局部移动集。我们在键角/扭转角空间中使用我们最近设计的链断裂/闭合(CBC)局部移动集,并对磷脂二棕榈酰磷脂酰胆碱(DPPC)采用恒定键长近似(CBLA)。通过计算分子能量和熵,我们证明了单个DPPC分子的快速构象平衡。我们还通过CBC局部移动MC方法展示了从类晶体到流体DPPC双层膜的转变,这由电子密度分布、头部基团取向、每个脂质的面积和整个脂质的位移表明。我们讨论了局部移动MC方法与分子动力学模拟相结合的潜力,例如用于研究含胆固醇的多组分脂质膜。