ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Importance of inter-residue interactions in ligand—receptor binding

Milan Senćanski and Ljiljana Došen-Mićović

Institute of Nuclear Sciences Vinca, Center for Multidisciplinary Research, University of Belgrade, Mihaila Petroviéa Alasa 1f-16, P.O. Box 522, 11001 Belgrade, Serbia

E-mail: sencanski@vin.bg.ac.rs

Abstract: In the present study, the role of inter-residue interactions in ligand binding and the ligand-receptor interactions were examined. Computational chemistry methods of ligand docking and molecular dynamics simulations were used to study the binding of β-funaltrexamine (β-FNA) and N-methyl-β-funaltrexamine (N-methyl-β-FNA) to μ- and κ-opioid receptors and to the μ-receptor with Lys303^6.58Glu mutation. It was found that inter-residue interactions Lys233^5.39-Glu303^6.58 in the mutant receptor and Lys227^5.39-Asp223^5.35 in the κ-receptor are more likely to prevent covalent bond formation between β-FNA and the receptor than the ligand-receptor interactions. This emphasizes the importance of inter-residue interactions in ligand binding as well as the effects of point-mutations.

Keywords: inter-residue interactions – opioid receptors – molecular docking – molecular dynamics – β-funaltrexamine

Full paper is available at www.springerlink.com.

DOI: 10.1515/chempap-2016-0017

Chemical Papers 70 (7) 994–1002 (2016)