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A computational prospect to aspirin side effects: Aspirin and COX-1 interaction analysis based on non-synonymous SNPs

Paper ID Volume ID Publish Year Pages File Format Full-Text
15121 1379 2014 6 PDF Available
Title
A computational prospect to aspirin side effects: Aspirin and COX-1 interaction analysis based on non-synonymous SNPs
Abstract

A computational prospect to aspirin side effects: aspirin and COX-1 interaction analysis based on non-synonymous SNPs•Modeling of human COX-1 was accomplished by using sheep Ovisaries COX-1.•Docking of flexible aspirin and rigid COX-1 monomer was performed.•The best binding position of aspirin within COX-1 binding site was theoretically analyzed.•The impact of COX-1 nsSNPs on aspirin inhibition potency is rated by calculation of Amber scores.•Expected severity of aspirin side effects in individuals was predicted by their COX-1 nsSNPs Amber scores.

Aspirin (ASA) is a commonly used nonsteroidal anti-inflammatory drug (NSAID), which exerts its therapeutic effects through inhibition of cyclooxygenase (COX) isoform 2 (COX-2), while the inhibition of COX-1 by ASA leads to apparent side effects. In the present study, the relationship between COX-1 non-synonymous single nucleotide polymorphisms (nsSNPs) and aspirin related side effects was investigated. The functional impacts of 37 nsSNPs on aspirin inhibition potency of COX-1 with COX-1/aspirin molecular docking were computationally analyzed, and each SNP was scored based on DOCK Amber score. The data predicted that 22 nsSNPs could reduce COX-1 inhibition, while 15 nsSNPs showed increasing inhibition level in comparison to the regular COX-1 protein. In order to perform a comparing state, the Amber scores for two Arg119 mutants (R119A and R119Q) were also calculated. Moreover, among nsSNP variants, rs117122585 represented the closest Amber score to R119A mutant. A separate docking computation validated the score and represented a new binding position for ASA that acetyl group was located within the distance of 3.86 Å from Ser529 OH group. This could predict an associated loss of activity of ASA through this nsSNP variant. Our data represent a computational sub-population pattern for aspirin COX-1 related side effects, and provide basis for further research on COX-1/ASA interaction.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideNon-synonymous SNPs would provide different protein structures that could differ in belong binding affinity. By protein modeling, docking and Amber score estimation, we computationally predict interaction of nsSNP variants of COX-1 and aspirin. This prediction indicates the pattern of COX-1 related side effects of aspirin in individuals containing different nsSNPs that would supplies basic data for future personalized medicine researches.

Keywords
Aspirin; COX-1; nsSNP; Amber score
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A computational prospect to aspirin side effects: Aspirin and COX-1 interaction analysis based on non-synonymous SNPs
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Publisher
Database: Elsevier - ScienceDirect
Journal: Computational Biology and Chemistry - Volume 51, August 2014, Pages 57–62
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us