Studying enzyme enantioselectivity using combined ab initio and free energy calculations: α-chymotrypsin and methyl cis- and trans-5-oxo-2-pentylpirrolidine-3-carboxylates

Autor:	Sabrina Pricl, Giuliana Pitacco, Marco Ferrone, Ennio Valentin, Fulvia Felluga, A. Coslanich, Maurizio Fermeglia
Rok vydání:	2003
Předmět:	Chymotrypsin biology Chemistry Implicit solvation Organic Chemistry Solvation Ab initio Substrate (chemistry) Catalysis Inorganic Chemistry Molecular dynamics Computational chemistry biology.protein Physical and Theoretical Chemistry Enantiomer Cis–trans isomerism
Zdroj:	Tetrahedron: Asymmetry. 14:3385-3399
ISSN:	0957-4166
DOI:	10.1016/j.tetasy.2003.09.003
Popis:	The application of a computational approach, based on molecular dynamics (MD) simulations and quantum mechanical-free energy (QM-FE) calculations, to explain the different substrate specificity and enantioselectivity of -chy- motrypsin (-CT) in the hydrolysis of methyl cis -a ndtrans-5-oxo-2-pentylpirrolidine-3-carboxylates is described. By applying a combination of molecular mechanics energy derived from MD simulations in explicit solvent, and solvation free energy derived from a continuum solvation model, we have calculated reasonable absolute free energies of binding (Gbind) for each -CT/enantiomer complex formation, and elucidated the balanced nature of the factors contributing to Gbind. Furthermore, our calculations based on QM-FE techniques have yielded an insight into the major issues affecting the observed enantioselectivity in the hydrolysis of substrate ester bonds by -chymotrypsin. © 2003 Elsevier Ltd. All rights reserved.
Databáze:	OpenAIRE
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