Philippine Science Letters
vol. 5 | no. 1 | 2012
published online January 13, 2012


Homology modelling and comparative docking analysis of two naturally occurring pancreatic glucokinase mutants

by Jose Isagani B. Janairo1,3 and Gerardo C. Janairo2,3

1Physics Department, College of Science
2Chemistry Department, College of Science
3Center for Natural Sciences and Environmental Research (CENSER), College of Science
De La Salle University, 2401 Taft Avenue, Manila 1004, Philippines



The homology models of two naturally occurring pancreatic glucokinase mutants with contrasting enzymatic behaviours were successfully generated and accurately predicted. The homology models of the activated V367M and deactivated R369P mutants were used for comparative docking analysis in order to probe why such mutations led to either an increase or diminishment of enzyme activity. Results of structural characterization and docking simulations suggest that the small conformational changes are responsible for the observed variation in enzymatic activity. Iterative fitting and comparison of their respective Ramachandran plots reveal that these conformational changes are not sufficient to perturb the overall protein architecture. However, active site modelling showed that these conformational changes altered the manner of ligand binding, from which the observed contrasting enzymatic behaviours originate.

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Submitted: November 24, 2011
Accepted: November 28, 2011
Published: January 13, 2012
Editor-in-charge: Eduardo A. Padlan
Eduardo A. Padlan