Virtual screening of m3 protein antagonists for finding a model to study the gammaherpesvirus damaged immune system and chemokine related diseases.
BACKGROUND
M3 protein is a chemokine decoy receptor involved in pathogenesis of persistent infection with gammaherpesvirus and complications related to the latency of this pathogen. We proposed that antagonists of the M3 would provide a unique opportunity for studying new therapeutic strategies in disordered immune system, immune-deficient states and role of chemokines in pathogenesis development.


METHODS
Comparative modeling and fold recognition algorithms have been used for prediction of M3 protein 3-D model. Evaluation of the models using Q-mean and ProSA-web score, has led to choosing predicted model by fold recognition algorithm as the best model which was minimized regarding energy level using Molegro Virtual Docker 2011.4.3.0 (MVD) software. Pockets and active sites of model were recognized using MVD cavity detection, and MetaPocket algorithms. Ten thousand compounds accessible on KEGG database were screened; MVD was used for computer simulated docking study; MolDock SE was selected as docking scoring function and final results were evaluated based on MolDock and Re-rank score.


RESULTS
Docking data suggested that prilocaine, which is generally applied as a topical anesthetic, binds strongly to 3-D model of M3 protein.


CONCLUSIONS
This study proposes that prilocaine is a potential inhibitor of M3 protein and possibly has immune enhancing properties.
Young Researchers and Elite Club, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
Ibrahim
I
Torktaz
Isfahan Cardiovascular Research Center, Isfahan cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
Mohaddeseh
M
Behjati
National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran ; Department of Clinical Biochemistry, Tarbiat Modares University, Tehran, Iran.
Sareh
S
Arjmand
Chemokine receptors; Docking; M3 protein; Murine gammaherpesvirus 68; Prilocaine