Molecular Dynamic Simulation of the Porcine Pancreatic Lipase in Non-aqueous Organic Solvents.

Zi-Shi Chen,Yu-Jia Liu,Jie Zhu,Yong-Si Lv,Shi-Lin Cao,Jin-Heng Hao,Wen-Hao Jiang,Kang-Ping He,Yi-Da Wu,Mei-Jie Xiong

doi:10.3389/fbioe.2020.00676

Abstract

This paper investigates the conformational stability of porcine pancreatic lipase (PPL) in three non-aqueous organic solvents, including dimethyl sulfoxide (DMSO), propylene glycol (PRG), and ethanol (EtOH) through molecular dynamic (MD) simulation. The root mean square deviations (RMSDs), radius of gyration (Rg), solution accessible surface area (SASA), radial distribution function (RDF), hydrogen bond (H-bond), Ramachandran plot analysis, secondary structure, and enzyme substrate affinity of the PPL in the various organic solvents were comparatively investigated. The results showed that the backbone and active pocket RMSD, and hydrophilic ASA of PPL in three solvents increase with the increase in the solvent LogP, while the Rg, hydrophobic ASA, and H-bond between the solvent and PPL decrease. Among the three organic solvents, DMSO acts as a better solvent, in which the PPL can be loose and extended, and retains its native backbone in DMSO compared to PRG and EtOH. Moreover, Ramachandran plot analysis indicated that the PPL structure quality in DMSO was higher than that in PRG and EtOH. Also, the molecular docking results showed that PPL in DMSO exhibited the highest enzyme-substrate affinity.

Highlights

Porcine pancreatic lipase (PPL) is widely used in many industrial fields because of its high enantioselectivity in biocatalysis (Li et al, 2017)
The effect of the three organic solvents, dimethyl sulfoxide (DMSO), propylene glycol (PRG), and ethanol (EtOH), on the conformational change of porcine pancreatic lipase (PPL) structure was studied by using molecular dynamic (MD) simulation, in order to give a molecular insight of the PPL structure in the organic solvent
The results showed that the total number of hydrogen bond (H-bond) between the solvent and enzyme decreased with the increase in the organic solvent’s hydrophobicity

Summary

INTRODUCTION

Porcine pancreatic lipase (PPL) is widely used in many industrial fields because of its high enantioselectivity in biocatalysis (Li et al, 2017). The conformational feature of lipase in organic solvents and the mechanism of the effects of solvents on the structure and catalytic performance of the enzyme still await further study. In order to obtain high-performance CgKR1mutants, Zheng et al identified two key residues (Phe and Phe94) by using MD simulation, molecular mechanics Poisson–Boltzmann (generalized born) surface area method, and molecular docking, and the result indicated that the higher binding affinity between the substrate and enzyme mutants was partially responsible for the improved catalytic enzyme activity. The conformations of Candida antarctica lipase B in several organic solvents were investigated by molecular simulation previously (Li et al, 2010), but few studies have been focused on PPL. The effect of the three organic solvents, DMSO, propylene glycol (PRG), and ethanol (EtOH), on the conformational change of PPL structure was studied by using MD simulation, in order to give a molecular insight of the PPL structure in the organic solvent

MATERIALS AND METHODS

CONCLUSION

DATA AVAILABILITY STATEMENT