Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, United Kingdom.
Departement de Chimie, Ecole Normale Superieure , 24 rue Lhomond, 75231 Paris Cedex 05, France.
J Chem Theory Comput. 2011 Jun 14;7(6):1951-61. doi: 10.1021/ct100715x. Epub 2011 May 4.
Absolute pKa values of the amino acid side chains of arginine, aspartate, cysteine, histidine, and tyrosine; the C- and N-terminal group of tyrosine; and the tryptophan radical cation are calculated using a revised density functional based molecular dynamics simulation technique introduced previously [ Cheng , J. ; Sulpizi , M. ; Sprik , M. J. Chem. Phys. 2009 , 131 , 154504 ]. In the revised scheme, acid deprotonation is considered as a dissociation rather than a proton transfer reaction, and a correction term for treating the proton as a hydronium ion is suggested. The acidity constants of the amino acids are obtained from the vertical energy gaps for removal or insertion of the acidic proton and the computed solvation free energy of the proton. The unsigned mean error relative to experimental results is 2.1 pKa units with a maximum error of 4.0 pKa units. The estimated mean statistical uncertainty due to the finite length of the trajectories is ±1.1 pKa units. The solvation structures of the protonated and deprotonated amino acids are analyzed in terms of radial distribution functions, which can serve as reference data for future force field developments.
使用先前介绍的修订后的基于密度泛函的分子动力学模拟技术[Cheng, J.; Sulpizi, M.; Sprik, M. J. Chem. Phys. 2009, 131, 154504]计算精氨酸、天冬氨酸、半胱氨酸、组氨酸和酪氨酸的氨基酸侧链的绝对 pk 值；酪氨酸的 C 和 N 末端基团；以及色氨酸自由基阳离子。在修订方案中，酸去质子化被认为是离解而不是质子转移反应，并提出了一个修正项来将质子处理为水合氢离子。通过从酸性质子的垂直能量间隙去除或插入来获得氨基酸的酸度常数，以及质子的计算溶剂化自由能。相对于实验结果的未签名平均误差为 2.1 pKa 单位，最大误差为 4.0 pKa 单位。由于轨迹的有限长度而引起的估计平均统计不确定性为±1.1 pKa 单位。根据径向分布函数分析质子化和去质子化氨基酸的溶剂化结构，可作为未来力场发展的参考数据。
