Insights on pH-dependent conformational changes of mosquito odorant binding proteins by molecular dynamics simulations

Abstract

Chemical recognition plays an important role for the survival and reproduction of many insect species. Odorant binding proteins (OBPs) are the primary components of the insect olfactory mechanism and have been documented to play an important role in the host-seeking mechanism of mosquitoes. They are “transport proteins” believed to transport odorant molecules from the external environment to their respective membrane targets, the olfactory receptors. The mechanism by which this transport occurs in mosquitoes remains a conundrum in this field. Nevertheless, OBPs have proved to be amenable to conformational changes mediated by a pH change in other insect species. In this paper, the effect of pH on the conformational flexibility of mosquito OBPs is assessed computationally using molecular dynamics simulations of a mosquito OBP “CquiOBP1” bound to its pheromone 3OG (PDB ID: 3OGN). Conformational twist of a loop, driven by a set of well-characterized changes in intramolecular interactions of the loop, is demonstrated. The concomitant (i) closure of what is believed to be the entrance of the binding pocket, (ii) expansion of what could be an exit site, and (iii) migration of the ligand towards this putative exit site provide preliminary insights into the mechanism of ligand binding and release of these proteins in mosquitoes. The correlation of our results with previous experimental observations based on NMR studies help us provide a cardinal illustration on one of the probable dynamics and mechanism by which certain mosquito OBPs could deliver their ligand to their membrane-bound receptors at specific pH conditions.

Keywords:

• odorant binding protein
• mosquito
• pH
• dynamics
• ligand binding

Acknowledgments

MM was supported by an international PhD fellowship from Conseil Regional de La Reunion in the framework of the joint dual-studentship program between Manipal University and University of La Réunion. RR is thankful to University of La Reunion for supporting this collaborative research through continuous invited professorship support since 2005. The authors are thankful to Manipal University, NCBS (TIFR) and Centre de Calcul of University of La Reunion for bioinformatics infrastructural support. We thank Prof N. Srinivasan (Indian Institute of Science), Prof Matthew (NCBS), Prof Frédéric Cadet (University of La Réunion), Prof Vinh Tran (University of Nantes), and Prof Sankararamakrishnan (IIT, Kanpur) for useful discussions regarding this work.