Biomolecular Chemical Simulations toward Elucidation of the Enantioselectivity and Reactivity of Lipases in Organic Synthesis

Chem-Bio Informatics Journal

Yoichiro Yagi¹  Makoto Kamezawa²  Takatomo Kimura²  Yoshinobu Naoshima³ 

[1]Department of Electrical and Electronic Engineering, Okayama University of Science

[2]Konan Chemical Industry Co., Ltd.

[3]Research Institute of Natural Sciences, Okayama University of Science

关键词: MD calculation;    分子動力学計算;    FMO calculation;    FMO計算;    lipase;    enantioselectivity;    鏡像体選択性;    reactivity;    反応性;    organic synthesis;    有機合成;    alcohol esters;    アルコール系エステル;    interaction energy;    相互作用;   

DOI  :  10.1273/cbij.18.21

学科分类：生物化学/生物物理

来源: Chem-Bio Informatics Society

【 摘 要 】

We are presently continuing to perform biomolecular chemical simulations for Burkholderia cepacia lipase (BCL) and Candida antarctica lipase typeB (CALB) to predict their enantioselectivity and reactivity toward various organic compounds. Here, we describe molecular dynamics (MD) and fragment molecular orbital (FMO) calculations on the complexes of CALB with primary and secondary alcohol esters. For esters with high enantioselectivity, the fast-reacting enantiomer of esters is located near the active site of CALB, whereas the slow-reacting enantiomer of esters moves away from the active site of CALB. On the other hand, for the esters with low enantioselectivity, we found that both (R)- and (S)-enantiomers of esters remain the active site of CALB. The FMO computations indicate that for the esters with high enantioselectivity, each fast-reacting enantiomer shows strong interactions with some particular amino acid residues, including Thr40, whereas for the esters with low enantioselectivity, both (R)- and (S)-enantiomers interact with identical amino acid residues including Thr40. It is predictable that Thr40 in CALB plays an important role in the chiral recognition of enantiomers through lipase-catalyzed biotransformations.

【 授权许可】

CC BY