Department of Chemistry, City College of the City University of New York, 160 Convent Avenue, New York, New York 10031, USA.
J Phys Chem B. 2011 Nov 24;115(46):13674-84. doi: 10.1021/jp2052213. Epub 2011 Nov 1.
Potentials of mean force (PMF) between ionizable amino acid side chains (Arg, Lys, His, Glu) in the headgroup area of a palmitoyl oleoyl phosphatidylcholine lipid bilayer were obtained from all-atom molecular dynamics simulations and the adaptive biasing force method. Simulations in bulk water were also performed for comparison. Side chains were constrained in collinear, stacking, and orthogonal (T-shaped) orientations. The most structured and attractive PMFs were observed for hydrogen-bonded side chains. Contact minima occurred at a distance of 2.6-3.1 Å between selected atoms or centers of mass with the most attractive interaction (-9.6 kcal/mol) observed between Arg(+) and Glu(-). Hydrogen bonds play a significant role in stabilizing these interactions. Interactions between like charged side chains can also be very attractive if the charges are screened by surrounding molecules or groups (e.g., the PMF value at the contact minimum for Arg(+)···Arg(+) is -7.6 kcal/mol). Like charged side chains can have contact minima as close as 3.6 Å. The PMFs depend strongly on the relative orientation of the side chains. In agreement with experimental studies and other simulations, we found the stacking arrangement of like charged side chains to be the most favorable orientation. Interaction energies and Lennard-Jones energies between side chains, headgroups, and water molecules were analyzed in order to rationalize the observed PMFs and their dependence on orientation. In general, the results cannot be explained by simple dielectric arguments.
从全原子分子动力学模拟和自适应偏见力方法中获得了带电荷氨基酸侧链（精氨酸、赖氨酸、组氨酸、谷氨酸）在棕榈酰油酰磷脂双层头部区域之间的平均力势（PMF）。还进行了在本体水中的模拟以进行比较。侧链被约束在共线、堆叠和正交（T 形）取向。在氢键结合的侧链中观察到最结构化和最具吸引力的 PMF。在选定原子或质心之间的距离为 2.6-3.1 Å 处出现接触最小值，观察到最具吸引力的相互作用（-9.6 kcal/mol）发生在 Arg(+) 和 Glu(-)之间。氢键在稳定这些相互作用中起着重要作用。如果电荷被周围的分子或基团屏蔽（例如，Arg(+)···Arg(+)的 PMF 值在接触最小值为-7.6 kcal/mol），带相同电荷的侧链之间的相互作用也可以非常有吸引力。带相同电荷的侧链之间的接触最小值可以接近 3.6 Å。PMF 强烈依赖于侧链的相对取向。与实验研究和其他模拟一致，我们发现带相同电荷的侧链的堆叠排列是最有利的取向。分析了侧链、头基和水分子之间的相互作用能和 Lennard-Jones 能，以解释观察到的 PMF 及其对取向的依赖性。一般来说，结果不能用简单的介电论点来解释。
