Valdeavella C V, Blatt H D, Yang L, Pettitt B M
Department of Chemistry, University of Houston, TX 77204-5641, USA.
Biopolymers. 1999 Aug;50(2):133-43. doi: 10.1002/(SICI)1097-0282(199908)50:2<133::AID-BIP2>3.0.CO;2-C.
The electrostatic potential and component dielectric constants from molecular dynamics (MD) trajectories of tuftsin, a tetrapeptide with the amino acid sequence Thr-Lys-Pro-Arg in water and in saline solution are presented. The results obtained from the analysis of the MD trajectories for the total electrostatic potential at points on a grid using the Ewald technique are compared with the solution to the Poisson-Boltzmann (PB) equation. The latter was solved using several sets of dielectric constant parameters. The effects of structural averaging on the PB results were also considered. Solute conformational mobility in simulations gives rise to an electrostatic potential map around the solute dominated by the solute monopole (or lowest order multipole). The detailed spatial variation of the electrostatic potential on the molecular surface brought about by the compounded effects of the distribution of water and ions close to the peptide, solvent mobility, and solute conformational mobility are not qualitatively reproducible from a reparametrization of the input solute and solvent dielectric constants to the PB equation for a single structure or for structurally averaged PB calculations. Nevertheless, by fitting the PB to the MD electrostatic potential surfaces with the dielectric constants as fitting parameters, we found that the values that give the best fit are the values calculated from the MD trajectories. Implications of using such field calculations on the design of tuftsin peptide analogues are discussed.
本文给出了促吞噬素（一种氨基酸序列为苏氨酸 - 赖氨酸 - 脯氨酸 - 精氨酸的四肽）在水和盐溶液中的分子动力学（MD）轨迹的静电势和组分介电常数。使用埃瓦尔德技术对网格上各点的总静电势进行MD轨迹分析得到的结果，与泊松 - 玻尔兹曼（PB）方程的解进行了比较。后者使用了几组介电常数参数进行求解。还考虑了结构平均对PB结果的影响。模拟中溶质构象迁移率产生了围绕溶质的静电势图，该图由溶质单极子（或最低阶多极子）主导。由靠近肽的水和离子分布、溶剂迁移率以及溶质构象迁移率的复合效应所导致的分子表面静电势的详细空间变化，对于单个结构或结构平均的PB计算，通过重新参数化输入溶质和溶剂的介电常数到PB方程无法定性地重现。然而，通过将PB与以介电常数为拟合参数的MD静电势表面进行拟合，我们发现给出最佳拟合的值是从MD轨迹计算得到的值。讨论了使用这种场计算对促吞噬素肽类似物设计的意义。
