Dataset Information

Analysis of the conformational stability and activity of Candida antarctica lipase B in organic solvents: insight from molecular dynamics and quantum mechanics/simulations.

ABSTRACT: The conformational stability and activity of Candida antarctica lipase B (CALB) in the polar and nonpolar organic solvents were investigated by molecular dynamics and quantum mechanics/molecular mechanics simulations. The conformation change of CALB in the polar and nonpolar solvents was examined in two aspects: the overall conformation change of CALB and the conformation change of the active site. The simulation results show that the overall conformation of CALB is stable in the organic solvents. In the nonpolar solvents, the conformation of the active site keeps stable, whereas in the polar solvents, the solvent molecules reach into the active site and interact intensively with the active site. This interaction destroys the hydrogen bonding between Ser(105) and His(224). In the solvents, the activation energy of CALB and that of the active site region were further simulated by quantum mechanics/molecular mechanics simulation. The results indicate that the conformation change in the region of active sites is the main factor that influences the activity of CALB.

SUBMITTER: Li C

PROVIDER: S-EPMC2937868 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Analysis of the conformational stability and activity of Candida antarctica lipase B in organic solvents: insight from molecular dynamics and quantum mechanics/simulations.

Li Cong C Tan Tianwei T Zhang Haiyang H Feng Wei W

The Journal of biological chemistry 20100703 37

The conformational stability and activity of Candida antarctica lipase B (CALB) in the polar and nonpolar organic solvents were investigated by molecular dynamics and quantum mechanics/molecular mechanics simulations. The conformation change of CALB in the polar and nonpolar solvents was examined in two aspects: the overall conformation change of CALB and the conformation change of the active site. The simulation results show that the overall conformation of CALB is stable in the organic solvent ...[more]

PMID: 20601697

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Project description:BackgroundThe Lipase Engineering Database (LED) integrates information on sequence, structure and function of lipases, esterases and related proteins with the alpha/beta hydrolase fold. A new superfamily for Candida antarctica lipase A (CALA) was introduced including the recently published crystal structure of CALA. Since CALA has a highly divergent sequence in comparison to other alpha/beta hydrolases, the Lipase Engineering Database was used to classify CALA in the frame of the already established classification system. This involved the comparison of CALA to similar structures as well as sequence-based comparisons against the content of the LED.ResultsThe new release 3.0 (December 2009) of the Lipase Engineering Database contains 24783 sequence entries for 18585 proteins as well as 656 experimentally determined protein structures, including the structure of CALA. In comparison to the previous release 1 with 4322 protein and 167 structure entries this update represents a significant increase in data volume. By comparing CALA to representative structures from all superfamilies, a structure from the deacetylase superfamily was found to be most similar to the structure of CALA. While the alpha/beta hydrolase fold is conserved in both proteins, the major difference is found in the cap region. Sequence alignments between both proteins show a sequence similarity of only 15%. A multisequence alignment of both protein families was used to create hidden Markov models for the cap region of CALA and showed that the cap region of CALA is unique among all other proteins of the alpha/beta hydrolase fold. By specifically comparing the substrate binding pocket of CALA to other binding pockets of alpha/beta hydrolases, the binding pocket of Candida rugosa lipase was identified as being highly similar. This similarity also applied to the lid of Candida rugosa lipase in comparison to the potential lid of CALA.ConclusionThe LED serves as a valuable tool for the systematic analysis of single proteins or protein families. The updated release 3.0 was used for the evaluation of alpha/beta hydrolases. The HTML version of the database with new features is available at http://www.led.uni-stuttgart.de and provides sequences, structures and a set of analysis tools including phylogenetic trees and HMM profiles.

Project description:Direct molecular dynamics (MD) simulation with ab initio quantum mechanical and molecular mechanical (QM/MM) methods is very powerful for studying the mechanism of chemical reactions in a complex environment but also very time-consuming. The computational cost of QM/MM calculations during MD simulations can be reduced significantly using semiempirical QM/MM methods with lower accuracy. To achieve higher accuracy at the ab initio QM/MM level, a correction on the existing semiempirical QM/MM model is an attractive idea. Recently, we reported a neural network (NN) method as QM/MM-NN to predict the potential energy difference between semiempirical and ab initio QM/MM approaches. The high-level results can be obtained using neural network based on semiempirical QM/MM MD simulations, but the lack of direct MD samplings at the ab initio QM/MM level is still a deficiency that limits the applications of QM/MM-NN. In the present paper, we developed a dynamic scheme of QM/MM-NN for direct MD simulations on the NN-predicted potential energy surface to approximate ab initio QM/MM MD. Since some configurations excluded from the database for NN training were encountered during simulations, which may cause some difficulties on MD samplings, an adaptive procedure inspired by the selection scheme reported by Behler [ Behler Int. J. Quantum Chem. 2015 , 115 , 1032 ; Behler Angew. Chem., Int. Ed. 2017 , 56 , 12828 ] was employed with some adaptions to update NN and carry out MD iteratively. We further applied the adaptive QM/MM-NN MD method to the free energy calculation and transition path optimization on chemical reactions in water. The results at the ab initio QM/MM level can be well reproduced using this method after 2-4 iteration cycles. The saving in computational cost is about 2 orders of magnitude. It demonstrates that the QM/MM-NN with direct MD simulations has great potentials not only for the calculation of thermodynamic properties but also for the characterization of reaction dynamics, which provides a useful tool to study chemical or biochemical systems in solution or enzymes.

Dataset Information

Analysis of the conformational stability and activity of Candida antarctica lipase B in organic solvents: insight from molecular dynamics and quantum mechanics/simulations.

Publications

Analysis of the conformational stability and activity of Candida antarctica lipase B in organic solvents: insight from molecular dynamics and quantum mechanics/simulations.

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