Polymorphism in the ligand binding domain of rage alters its binding affinity towards Aβ42 peptides: an in-silico study Online publication date: Tue, 09-Aug-2016
by Sreeram Krishnan; P. Rani
International Journal of Bioinformatics Research and Applications (IJBRA), Vol. 12, No. 3, 2016
Abstract: The study was aimed to understand the influence of RAGE polymorphism (G82S, R48Q, R77C) on the binding affinity to Aβ42 peptides through an in-silico approach. The structure of RAGE ectodomain (3CJJ) was docked with three forms of Aβ42 [monomeric: apolar environment (1IYT), polar environment (1Z0Q) and fibrillar (2BEG)] using CLUSPRO in antibody mode. Highest binding score was observed with 2BEG indicating enhanced affinity of RAGE towards fibrillar Aβ42. Amino acid modifications were done in RAGE sequence to create variants and their structures were generated using SWISS MODEL followed by molecular dynamics simulation in GROMACS. The lowest energy structures (10 nos.) were then docked with Aβ42 peptides. Compared to wtRAGE, G82S variant showed higher affinity whereas R48Q variant showed lesser affinity to all three forms of Aβ42. R77C variant showed significant decrease in affinity compared to wtRAGE when docked with 1IYT, and increased affinity with the other forms. The results of the study indicate that RAGE polymorphisms could modify the affinity of RAGE towards Aβ42.
Online publication date: Tue, 09-Aug-2016
If you are not a subscriber and you just want to read the full contents of this article, buy online access here.Complimentary Subscribers, Editors or Members of the Editorial Board of the International Journal of Bioinformatics Research and Applications (IJBRA):
Login with your Inderscience username and password:
Want to subscribe?
A subscription gives you complete access to all articles in the current issue, as well as to all articles in the previous three years (where applicable). See our Orders page to subscribe.
If you still need assistance, please email email@example.com