In silico analysis predicting effects of deleterious SNPs of human RASSF5 gene on its structure and functions

Abstract Ras association domain-containing protein 5 (RASSF5), one of the prospective biomarkers for tumors, generally plays a crucial role as a tumor suppressor. As deleterious effects can result from functional differences through SNPs, we sought to analyze the most deleterious SNPs of RASSF5 as w...

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Autores principales:	Md. Shahadat Hossain, Arpita Singha Roy, Md. Sajedul Islam
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc6fb4d1282146989c086243d6fccdde
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spelling	oai:doaj.org-article:cc6fb4d1282146989c086243d6fccdde2021-12-02T19:09:19ZIn silico analysis predicting effects of deleterious SNPs of human RASSF5 gene on its structure and functions10.1038/s41598-020-71457-12045-2322https://doaj.org/article/cc6fb4d1282146989c086243d6fccdde2020-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-71457-1https://doaj.org/toc/2045-2322Abstract Ras association domain-containing protein 5 (RASSF5), one of the prospective biomarkers for tumors, generally plays a crucial role as a tumor suppressor. As deleterious effects can result from functional differences through SNPs, we sought to analyze the most deleterious SNPs of RASSF5 as well as predict the structural changes associated with the mutants that hamper the normal protein–protein interactions. We adopted both sequence and structure based approaches to analyze the SNPs of RASSF5 protein. We also analyzed the putative post translational modification sites as well as the altered protein–protein interactions that encompass various cascades of signals. Out of all the SNPs obtained from the NCBI database, only 25 were considered as highly deleterious by six in silico SNP prediction tools. Among them, upon analyzing the effect of these nsSNPs on the stability of the protein, we found 17 SNPs that decrease the stability. Significant deviation in the energy minimization score was observed in P350R, F321L, and R277W. Besides this, docking analysis confirmed that P350R, A319V, F321L, and R277W reduce the binding affinity of the protein with H-Ras, where P350R shows the most remarkable deviation. Protein–protein interaction analysis revealed that RASSF5 acts as a hub connecting two clusters consisting of 18 proteins and alteration in the RASSF5 may lead to disassociation of several signal cascades. Thus, based on these analyses, our study suggests that the reported functional SNPs may serve as potential targets for different proteomic studies, diagnosis and therapeutic interventions.Md. Shahadat HossainArpita Singha RoyMd. Sajedul IslamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Md. Shahadat Hossain Arpita Singha Roy Md. Sajedul Islam In silico analysis predicting effects of deleterious SNPs of human RASSF5 gene on its structure and functions
description	Abstract Ras association domain-containing protein 5 (RASSF5), one of the prospective biomarkers for tumors, generally plays a crucial role as a tumor suppressor. As deleterious effects can result from functional differences through SNPs, we sought to analyze the most deleterious SNPs of RASSF5 as well as predict the structural changes associated with the mutants that hamper the normal protein–protein interactions. We adopted both sequence and structure based approaches to analyze the SNPs of RASSF5 protein. We also analyzed the putative post translational modification sites as well as the altered protein–protein interactions that encompass various cascades of signals. Out of all the SNPs obtained from the NCBI database, only 25 were considered as highly deleterious by six in silico SNP prediction tools. Among them, upon analyzing the effect of these nsSNPs on the stability of the protein, we found 17 SNPs that decrease the stability. Significant deviation in the energy minimization score was observed in P350R, F321L, and R277W. Besides this, docking analysis confirmed that P350R, A319V, F321L, and R277W reduce the binding affinity of the protein with H-Ras, where P350R shows the most remarkable deviation. Protein–protein interaction analysis revealed that RASSF5 acts as a hub connecting two clusters consisting of 18 proteins and alteration in the RASSF5 may lead to disassociation of several signal cascades. Thus, based on these analyses, our study suggests that the reported functional SNPs may serve as potential targets for different proteomic studies, diagnosis and therapeutic interventions.
format	article
author	Md. Shahadat Hossain Arpita Singha Roy Md. Sajedul Islam
author_facet	Md. Shahadat Hossain Arpita Singha Roy Md. Sajedul Islam
author_sort	Md. Shahadat Hossain
title	In silico analysis predicting effects of deleterious SNPs of human RASSF5 gene on its structure and functions
title_short	In silico analysis predicting effects of deleterious SNPs of human RASSF5 gene on its structure and functions
title_full	In silico analysis predicting effects of deleterious SNPs of human RASSF5 gene on its structure and functions
title_fullStr	In silico analysis predicting effects of deleterious SNPs of human RASSF5 gene on its structure and functions
title_full_unstemmed	In silico analysis predicting effects of deleterious SNPs of human RASSF5 gene on its structure and functions
title_sort	in silico analysis predicting effects of deleterious snps of human rassf5 gene on its structure and functions
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/cc6fb4d1282146989c086243d6fccdde
work_keys_str_mv	AT mdshahadathossain insilicoanalysispredictingeffectsofdeleterioussnpsofhumanrassf5geneonitsstructureandfunctions AT arpitasingharoy insilicoanalysispredictingeffectsofdeleterioussnpsofhumanrassf5geneonitsstructureandfunctions AT mdsajedulislam insilicoanalysispredictingeffectsofdeleterioussnpsofhumanrassf5geneonitsstructureandfunctions
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In silico analysis predicting effects of deleterious SNPs of human RASSF5 gene on its structure and functions

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