4.6 Article

Computational analysis of deleterious single nucleotide polymorphisms in catechol O-Methyltransferase conferring risk to post-traumatic stress disorder

Journal

JOURNAL OF PSYCHIATRIC RESEARCH
Volume 138, Issue -, Pages 207-218

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jpsychires.2021.03.048

Keywords

(COMT); Molecular dynamic simulations (MD; simulations); Single nucleotide polymorphism (SNP); Molecular modelling; Mutation

Categories

Funding

  1. NIH [R01AI129788]
  2. TUFCCC/HC Regional Comprehensive Cancer Health Disparity Partnership
  3. National Cancer Institute of National Institutes of Health (NCI/NIH) [U54 CA221704(5)]

Ask authors/readers for more resources

This study analyzed the impact of deleterious SNPs in the COMT gene associated with PTSD using computational approaches and molecular dynamic simulations. The SNP rs4680 (V158M) in COMT was found to have a deleterious effect on PTSD. Results from molecular dynamics simulations showed significant structural fluctuations between wild-type and mutant forms of the COMT protein.
Post-traumatic stress disorder (PTSD) is one of the prevalent neurological disorder which is drawing increased attention over the past few decades. Major risk factors for PTSD can be categorized into environmental and genetic factors. Among the genetic risk factors, polymorphisms in the catechol-O-methyltransferase (COMT) gene is known to be associated with the risk for PTSD. In the present study, we analysed the impact of deleterious single nucleotide polymorphisms (SNPs) in the COMT gene conferring risk to PTSD using computational based approaches followed by molecular dynamic simulations. The data on COMT gene associated with PTSD were collected from several databases including Online Mendelian Inheritance in Man (OMIM) search. Datasets related to SNP were downloaded from the dbSNP database. To study the structural and dynamic effects of COMT wild type and mutant forms, we performed molecular dynamics simulations (MD simulations) at a time scale of 300 ns. Results from screening the SNPs using the computational tools SIFT and Polyphen-2 demonstrated that the SNP rs4680 (V158M) in COMT has a deleterious effect with phenotype in PTSD. Results from the MD simulations showed that there is some major fluctuations in the structural features including root mean square deviation (RMSD), radius of gyration (Rg), root mean square fluctuation (RMSF) and secondary structural elements including alpha-helices, sheets and turns between wild-type (WT) and mutant forms of COMT protein. In conclusion, our study provides novel insights into the deleterious effects and impact of V158M mutation on COMT protein structure which plays a key role in PTSD.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available