Molecular orbital analysis of the catalytic process of serine proteinases: Effect of environment on protonation of the histidine aspartate diad of subtilisin

Applied quantum chemistry

“…In contrast, a strong electrostatic field exists, both inside and in the vicinity of proteins, which is produced by a-helices [339] or by charged or polar side chains. The theoretically estimated His-Asp proton transfer energy is 15-101 kJ/mol in the gas phase but this is drastically lowered (by -116 kJ/mol) to a value between -101 and -15 kJ/mol in the protein [983], i.e. the proton is located on the His side chain.…”

“…Owing to the formidable numerical difficulties hydration is mostly studied at a nonstatistical level using ab initio or semiempirical methods [273,581,983]. An example for such calculations, hydration of acetamide, is depicted in Fig.…”

“…Hydration considerably influences the acidity and basicity of different species as compared to the gas phase. This is illustrated by the protonation of carboxylate and imidazole [983]. Protonation energies of HCOO ~ and C3H4N 2 as calculated by the ab initio SCF method with a 4-31G basis set are 1487 and 1028 kJ/mol, respectively, that * is, formic acid is much less "acidic" in the gas phase than the imidazolium cation.…”

“…These effects are mostly electrostatic in nature so they can be studied relatively easily by theoretical methods [980]. The first calculations were published by Warshel and Levitt [1403] and by Hayes and Kollman [524]; these were followed by several other studies [339,983,1345].…”

“…the proton is located on the His side chain. The special importance of theoretical studies on such problems [339,983,1345] is to call attention to the limitations of biomimetic chemistry, the discipline where biomacromulecular processes are studied on small models.…”