Combined docking and molecular dynamics study of lipase catalyzed kinetic resolution of 1-phenylethanol in organic solvents

Abstract

A combined docking and molecular dynamics protocol was applied to investigate kinetic resolution of 1-phenylethanol using Burkholderia cepacia lipase (BCL) in different organic solvents. BCL has open structure compared to other lipases and is found to be more effective in kinetic resolution of primary and secondary alcohols compared to other lipases. The fundamental understanding of the difference in specificity of lipases in esterification/transesterification reactions in presence of solvents can help in reduction of experimental cost. In this work, solvents such as hexane, tert-butyl methyl ether, toluene and decalin were studied. The conformational changes in BCL structure were captured using molecular dynamics (MD) studies. The protein conformations from MD were used for docking studies to estimate ΔΔG between R and S form of tetrahedral intermediate. The predicted E value was compared with experimental data for hexane and good agreement was obtained. It was observed that hexane and toluene are better solvents for chiral resolution of 1-phenylethanol compared to tert-butyl methyl ether and decalin when lipase in free form is used. The MD simulations of R form of tetrahedral intermediate in solvents were carried out to study the critical bonds distances.