Center for Drug Design and Development, The University of Toledo, Toledo, Ohio 43606-3390, United States.
J Phys Chem B. 2010 Dec 16;114(49):16436-42. doi: 10.1021/jp103313s. Epub 2010 Nov 19.
Salt-bridge formation between Asp/Glu···Lys and Asp/Glu···Arg side chains has been studied by model systems including formic and acetic acids as proton donors and methylamine, guanidine, and methylguanidine as proton acceptors. Calculations have been performed up to the CCSD(T)(CBS)//MP2/aug-cc-pvtz level with formic acid proton donors. Complexes formed with acetic acid were studied at the CCSD(T)/aug-cc-pvdz//MP2/aug-cc-pvdz level. Protein environments of low and moderate polarity were mimicked by a continuum solvent with dielectric constants (ε) set to 5 and 15, respectively. Free energy differences, ΔG(tot), were calculated for the neutral, hydrogen-bonded form and for the tautomeric ion pair. These values predict that a salt bridge is not favored for the Asp/Glu···Lys pair, even in an environment with ε as large as 15. In contrast, the Asp/Glu···Arg salt bridge is feasible even in an environment with ε = 5. Charge transfers for the complexes were calculated on the basis of CHELPG and AIM charges.
已通过包括甲酸和乙酸作为质子供体以及甲胺、胍和甲基胍作为质子受体的模型体系研究了 Asp/Glu···Lys 和 Asp/Glu···Arg 侧链之间的盐桥形成。已在甲酸质子供体的情况下进行了最高达到 CCSD(T)(CBS)//MP2/aug-cc-pvtz 水平的计算。在 CCSD(T)/aug-cc-pvdz//MP2/aug-cc-pvdz 水平研究了与乙酸形成的复合物。通过介电常数（ε）分别设置为 5 和 15 的连续溶剂模拟低极性和中等极性的蛋白质环境。已计算中性、氢键合形式和互变异构离子对的自由能差ΔG(tot)。这些值表明，即使在 ε 高达 15 的环境中，盐桥也不有利于 Asp/Glu···Lys 对，而 Asp/Glu···Arg 盐桥在 ε = 5 的环境中也是可行的。已基于 CHELPG 和 AIM 电荷计算了复合物的电荷转移。
