Virtual binding of four selected inhibitors (KZ7088, MP576, HE602 and VE607) to sars coronavirus main proteinase using autodock software

Date

4-2005

Degree

Bachelor of Science in Chemistry

College

College of Arts and Sciences (CAS)

Adviser/Committee Chair

Alma O Gonzales

Abstract

Molecular docking of selected inhibitors (rigid or flexible ligands) to SARS coronavirus main proteinase was studied using AUTODOCK software. The three-dimensional structure of the SARS coronavirus main proteinase was obtained from the National Center for Biotechnology Information (NCBI) database and both monomeric and dimeric forms at pH 6.0 and 8.0 were used as receptors. The molecular structures of the selected SARS proteinase inhibitors (KZ7088, MP576, HE602, and VE607) were optimized using AMBER and PM3 methods (HYPERCHEM software). Genetic algorithm was used to calculate the Gibbs energy of binding (ΔGbinding) and docking energy (ΔEdocked). The receptor residues involved in ligand binding were identified based on calculated distances between residues and bound ligand. The computed ΔGbinding values for the inhibitors were more negative in the dimeric receptor compared to those for the monomeric form. Inhibitor binding increased with pH. The computed ΔGbinding values are also less negative in the flexible form compared to the rigid form. Among the four inhibitors, HE602 showed the greatest binding (ΔGbinding = -11.46 ± 0.07 kcaUmol) while KZ7088 was the least bound (ΔGbinding = -1.81 ± 0.07 kcaUmol). Significant mode of inhibition was also observed in MP576, since it acts as a competitive inhibitor in its flexible form. The mode of inhibition is affected by the flexibility of the ligand and the different kinds of interactions such as H-bonding, electrostatic and hydrophobic interactions. Three major binding sites were observed in the receptor - the substrate-binding site composed of His 41, His 164, Gln 189, Gly 143, Asn 142, Cys 145 and Ser 1; the second with Lys 137, Asn 238, Gly 238 and Thr 280; and the third with Tyr 118, Val 303, Asn 119 and Ser 123.

Language

English

Location

UPLB Main Library Special Collections Section (USCS)

Call Number

LG 993.5 2005 C4 M65

Document Type

Thesis

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