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MODELING OF PENICYLLINAMIDASE ENANTIOSELECTIVITY BY FREE ENERGY PERTURBATION

Zeifman A.A, Perepelkin V.V, Novikov F.N, Stroganov O.V, Chilov G.G
New free energy perturbation/molecular dynamics method for the calculation of enzymatic reactions enantioselectivity was proposed. Ratio of rate constants for two enantiomers is obtained by calculating free energy difference between initial enzyme-substrate complexes of both enantiomers and reaction transition states for both enantiomers, which together gives the difference in the activation energy. Free energy transition between enantiomers is achieved by planarizing the chiral carbon atoms. Proposed approach allows to account for all protein, solvent and ligand atoms and produces true free energy value due to averaging over the thermodynamic ensemble of states. It allowed not only to predict the direction of the enantioselectivity but gave numerical data which was in a good agreement with known experimental results for the hydrolysis of the chiral substrate by penicyllinamidase - 2-phenyl-N-(1-phenethyl)acetamide. In conjunction with existing methods for modeling of mutant enzyme structures, proposed approach will allow for a straightforward design of novel efficient biocatalyzers.

Библиографическая ссылка

Зейфман А.А, Перепёлкин В.В, Новиков Ф.Н, Строганов О.В, Чилов Г.Г МОДЕЛИРОВАНИЕ СТЕРЕОСЕЛЕКТИВНОСТИ ПЕНИЦИЛЛИНАМИДАЗЫ МЕТОДОМ ВОЗМУЩЕНИЯ СВОБОДНОЙ ЭНЕРГИИ // Научное обозрение. Химические науки. 2020. № 1. С. 14-14;
URL: https://science-chemistry.ru/en/article/view?id=10 (дата обращения: 27.07.2026).