Cherry L. Emerson Center for Scientific Computation and Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.
J Am Chem Soc. 2011 Mar 16;133(10):3625-34. doi: 10.1021/ja110425s. Epub 2011 Feb 22.
Mixed MD/MC simulation at fixed difference in chemical potential (Δμ) between two lipid types provides a computational indicator of the relative affinities of the two lipids for different environments. Applying this technique to ternary DPPC/DOPC/cholesterol bilayers yields a DPPC/DOPC ratio that increases with increasing cholesterol content at fixed Δμ, consistent with the known enrichment of DPPC and cholesterol-rich in liquid-ordered phase domains in the fluid-fluid coexistence region of the ternary phase diagram. Comparison of the cholesterol-dependence of PC compositions at constant Δμ with experimentally measured coexistence tie line end point compositions affords a direct test of the faithfulness of the atomistic model to experimental phase behavior. DPPC/DOPC ratios show little or no dependence on cholesterol content at or below 16% cholesterol in the DOPC-rich region of the composition diagram, indicating cooperativity in the favorable interaction between DPPC and cholesterol. The relative affinity of DPPC and DOPC for high cholesterol bilayer environments in simulations is explicitly shown to depend on the degree of cholesterol alignment with the bilayer normal, suggesting that a source of the cooperativity is the composition dependence of cholesterol tilt angle distributions.
在两种脂质之间的化学势（Δμ）固定差下进行混合 MD/MC 模拟，为两种脂质对不同环境的相对亲和力提供了计算指标。将该技术应用于 DPPC/DOPC/胆固醇三层膜，在固定的 Δμ 下，随着胆固醇含量的增加，DPPC/DOPC 比增加，这与在三元相图的流体-流体共存区域中已知的 DPPC 和富含胆固醇的有序相区域的富集一致。在恒定的 Δμ 下比较 PC 组成对胆固醇的依赖性与实验测量的共存 tie line 端点组成，直接检验了原子模型对实验相行为的忠实程度。在 DOPC 丰富区域的组成图中，胆固醇含量在 16%或以下时，DPPC/DOPC 比几乎没有或没有依赖于胆固醇含量，表明 DPPC 和胆固醇之间有利相互作用的协同性。在模拟中，DPPC 和 DOPC 对高胆固醇双层环境的相对亲和力明确取决于胆固醇与双层法线的对齐程度，表明协同性的一个来源是胆固醇倾斜角分布的组成依赖性。
