Structural Consequences of the Polymorphism Q223R in the Human Leptin Receptor: A Molecular Dynamics Study
- 1 Laboratory of Computational Biophysics and Biochemistry, Department of Molecular Biomedicine and Doctoral Program of Biotechnology, ENMH-IPN, Mexico City, Mexico
- 2 Department of Molecular Biomedicine and Doctoral Program of Biotechnology, ENMH-IPN, Mexico City, Mexico
- 3 Department of Neurosciences, National Institute of Perinatology “Isidro Espinosa de los Reyes” and Department of Mental Health, Faculty of Medicine, UNAM, Mexico City, Mexico
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.
DOI: https://doi.org/10.3844/ajabssp.2013.239.248
Copyright: © 2013 Jonathan P. Carrillo-Vázquez, Brenda Chimal-Vega, Beatriz Zamora-López, Laurence A. Marchat, Claudia G. Benítez-Cardoza, César A.S. Reyes-López and Absalom Zamorano-Carrillo. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Keywords
- Homology Modeling
- Molecular Dynamics
- Leptin Receptor
- Obesity
- Polymorphism