کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6490115 1416961 2018 33 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Prediction of enantioselectivity of lipase catalyzed kinetic resolution using umbrella sampling
ترجمه فارسی عنوان
پیش بینی انانتیوزلکتیویتی از رزونانس جنبش کاتالیزوری لیپاز با استفاده از نمونه گیری چتر
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
چکیده انگلیسی
Enantiopure intermediates are preferred for drug synthesis in pharmaceutical industry. Lipases are widely used for chiral resolution of optically active compounds based on kinetic resolution. In the kinetic resolution, two enantiomers react with different rates in presence of a chiral catalyst or reagent, resulting in obtaining one enantiomer of great excess compared to other. The enantiomeric ratio (E) is closely related to the free energy difference (ΔΔG) of the activated state of substrate enantiomers. Molecular dynamic (MD) simulations with umbrella sampling technique can be used for estimation of activation free energy change of enantiomers. In this work, lipase-catalyzed transesterification of racemic alcohols with single and double hydroxyl groups have been studied. The umbrella sampling studies have been carried out for Candida rugosa lipase and Burkholderia cepacia lipase in n-hexane. The distance between serine residue in the catalytic triad and the ligand has been considered as a reaction coordinate and various conformations have been selected for MD simulation. The E value has been estimated based on free energy change from umbrella sampling. The estimated E values are in good agreement with experimental data. The work highlights changes in lipase conformation in n-hexane, ligand-protein interaction as well as free energy curve as a function of the reaction coordinate.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Biotechnology - Volume 283, 10 October 2018, Pages 70-80
نویسندگان
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