In silico studies reveal structural deviations of mutant profilin-1 and interaction with riluzole and edaravone in amyotrophic lateral sclerosis

Abstract This study aimed to investigate four of the eight PFN-1 mutations that are located near the actin-binding domain and determine the structural changes due to each mutant and unravel how these mutations alter protein structural behavior. Swapaa’s command in UCSF chimera for generating mutatio...

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Autores principales:	Ahmad Shahir Sadr, Changiz Eslahchi, Alireza Ghassempour, Mahmoud Kiaei
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2a2e3ebd7d4744748b4f0ae4f27354b4
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spelling	oai:doaj.org-article:2a2e3ebd7d4744748b4f0ae4f27354b42021-12-02T16:35:56ZIn silico studies reveal structural deviations of mutant profilin-1 and interaction with riluzole and edaravone in amyotrophic lateral sclerosis10.1038/s41598-021-86211-42045-2322https://doaj.org/article/2a2e3ebd7d4744748b4f0ae4f27354b42021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86211-4https://doaj.org/toc/2045-2322Abstract This study aimed to investigate four of the eight PFN-1 mutations that are located near the actin-binding domain and determine the structural changes due to each mutant and unravel how these mutations alter protein structural behavior. Swapaa’s command in UCSF chimera for generating mutations, FTMAP were employed and the data was analyzed by RMSD, RMSF graphs, Rg, hydrogen bonding analysis, and RRdisMaps utilizing Autodock4 and GROMACS. The functional changes and virtual screening, structural dynamics, and chemical bonding behavior changes, molecular docking simulation with two current FDA-approved drugs for ALS were investigated. The highest reduction and increase in Rg were found to exist in the G117V and M113T mutants, respectively. The RMSF data consistently shows changes nearby to this site. The in silico data described indicate that each of the mutations is capable of altering the structure of PFN-1 in vivo. The potential effect of riluzole and edaravone two FDA approved drugs for ALS, impacting the structural deviations and stabilization of the mutant PFN-1 is evaluated using in silico tools. Overall, the analysis of data collected reveals structural changes of mutant PFN-1 protein that may explain the neurotoxicity and the reason(s) for possible loss and gain of function of PFN-1 in the neurotoxic model of ALS.Ahmad Shahir SadrChangiz EslahchiAlireza GhassempourMahmoud KiaeiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ahmad Shahir Sadr Changiz Eslahchi Alireza Ghassempour Mahmoud Kiaei In silico studies reveal structural deviations of mutant profilin-1 and interaction with riluzole and edaravone in amyotrophic lateral sclerosis
description	Abstract This study aimed to investigate four of the eight PFN-1 mutations that are located near the actin-binding domain and determine the structural changes due to each mutant and unravel how these mutations alter protein structural behavior. Swapaa’s command in UCSF chimera for generating mutations, FTMAP were employed and the data was analyzed by RMSD, RMSF graphs, Rg, hydrogen bonding analysis, and RRdisMaps utilizing Autodock4 and GROMACS. The functional changes and virtual screening, structural dynamics, and chemical bonding behavior changes, molecular docking simulation with two current FDA-approved drugs for ALS were investigated. The highest reduction and increase in Rg were found to exist in the G117V and M113T mutants, respectively. The RMSF data consistently shows changes nearby to this site. The in silico data described indicate that each of the mutations is capable of altering the structure of PFN-1 in vivo. The potential effect of riluzole and edaravone two FDA approved drugs for ALS, impacting the structural deviations and stabilization of the mutant PFN-1 is evaluated using in silico tools. Overall, the analysis of data collected reveals structural changes of mutant PFN-1 protein that may explain the neurotoxicity and the reason(s) for possible loss and gain of function of PFN-1 in the neurotoxic model of ALS.
format	article
author	Ahmad Shahir Sadr Changiz Eslahchi Alireza Ghassempour Mahmoud Kiaei
author_facet	Ahmad Shahir Sadr Changiz Eslahchi Alireza Ghassempour Mahmoud Kiaei
author_sort	Ahmad Shahir Sadr
title	In silico studies reveal structural deviations of mutant profilin-1 and interaction with riluzole and edaravone in amyotrophic lateral sclerosis
title_short	In silico studies reveal structural deviations of mutant profilin-1 and interaction with riluzole and edaravone in amyotrophic lateral sclerosis
title_full	In silico studies reveal structural deviations of mutant profilin-1 and interaction with riluzole and edaravone in amyotrophic lateral sclerosis
title_fullStr	In silico studies reveal structural deviations of mutant profilin-1 and interaction with riluzole and edaravone in amyotrophic lateral sclerosis
title_full_unstemmed	In silico studies reveal structural deviations of mutant profilin-1 and interaction with riluzole and edaravone in amyotrophic lateral sclerosis
title_sort	in silico studies reveal structural deviations of mutant profilin-1 and interaction with riluzole and edaravone in amyotrophic lateral sclerosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2a2e3ebd7d4744748b4f0ae4f27354b4
work_keys_str_mv	AT ahmadshahirsadr insilicostudiesrevealstructuraldeviationsofmutantprofilin1andinteractionwithriluzoleandedaravoneinamyotrophiclateralsclerosis AT changizeslahchi insilicostudiesrevealstructuraldeviationsofmutantprofilin1andinteractionwithriluzoleandedaravoneinamyotrophiclateralsclerosis AT alirezaghassempour insilicostudiesrevealstructuraldeviationsofmutantprofilin1andinteractionwithriluzoleandedaravoneinamyotrophiclateralsclerosis AT mahmoudkiaei insilicostudiesrevealstructuraldeviationsofmutantprofilin1andinteractionwithriluzoleandedaravoneinamyotrophiclateralsclerosis
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In silico studies reveal structural deviations of mutant profilin-1 and interaction with riluzole and edaravone in amyotrophic lateral sclerosis

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