Structural consequences of the polymorphism Q223R in the human leptin receptor: A molecular dynamics study

Abstract

Leptin Receptor (LEPR) is a component of a signaling pathway related to appetite and energy expenditure. Single Nucleotide Polymorphisms (SNP) of Leptin receptor gene (lepr) have been proposed as possible modulator of adipose tissue and body weight. The main phenomenological consequence reported of these SNPs is the modulation of the LEP-LEPR interaction promoting the weight gain. Particularly, Q223R polymorphism has been associated with human obesity in some populations. In this work, we analyze the structural effects of Q223R substitution in a model of the extracellular region of LEPR comparing the stability between LEPR-Q and its Q223R variant (rs1137101) by Molecular Dynamics (MD) simulations. These results showed different behavior between both molecules after one nanosecond (ns) of simulation and significant differences in the secondary structure content were evidenced. © 2013 Science Publication.