Molecular Simulation Investigation of Prolyl Oligopeptidase from Pyrobaculum Calidifontis and In Silico Docking With Substrates and Inhibitors

Volume 2 - Issue 4

Hira Amjad¹, Waqar Hussain² and Nouman Rasool³*

Received: May 23, 2018;   Published: May 31, 2018

DOI: 10.32474/OAJBEB.2018.02.000141

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Abstract

Prolyl oligopeptidase is an important enzyme known to be involved in many human diseases including Alzheimer disease, Parkinson disease and dementia. Microbial world is rich with many diversified enzymes which can be studied as analogous to eukaryotic counter parts. Genome survey of Pyrobaculum calidifontis revealed that three prolyl oligopeptidase with ORFs P_cal 0773; P_cal 1307 and P_cal 1997 are present in this microbe while none of these have been studied. In this study, molecular modeling and in silico characterization of the enzyme prolyl oligopeptidase (P_cal 0773) is performed. The tertiary structure of the enzyme has conserved residues Ser431, Asp513 and His 545 at active site. The structure was observed to have two domains which were α/β hydrolase fold and β-propeller. Where β-propeller domain, most specific feature of Propyl oligopeptidase, is comprised of seven blades constituted by β sheets. The predicted structure was refined using molecular dynamics and docked with two substrates and five inhibitor at catalytic site which showed affinity with the catalytic residues and also forms bond with functional groups of other amino acids present in substrate binding pocket. Among the five inhibitors, three are conventional while two novel inhibitors are also predicted which has different mode of activity for inhibition.

Keywords: Prolyl oligopeptidase; Pyrobaculum calidifontis; β-propeller; Molecular Dynamics; enzymes-substrate complex

Abbrevations: GROMACS: Groningen Machine for Chemical Simulations; OPLS-AA: Optimized Potential for Liquid Simulation; EM: Energy Minimization; NVT: Number Volume and Temperature; NPT: Number Pressure and Temperature; PWE: Particle Mesh Ewald; LINCS: Linear Constraint Solver; GRACE: Graphing Advanced Computation and Exploration; VMD: Visual Molecular Dynamics

Abstract| Introduction| Materials and Methods| Results and Discussion| Conclusion| References|