“School of Biological Sciences”

Back to Papers Home
Back to Papers of School of Biological Sciences

Paper   IPM / Biological Sciences / 16681
School of Biological Sciences
  Title:   In silico studies reveal structural deviations of mutant profilin-1 and interaction with riluzole and edaravone in amyotrophic lateral sclerosis
  Author(s): 
1.  Ahmad Shahir Sadr
2.  Changiz Eslahchi
3.  Alireza Ghassempour
4.  Mahmoud Kiaei
  Status:   Published
  Journal: Scientific Reports
  No.:  1
  Vol.:  11
  Year:  2021
  Pages:   1-14
  Supported by:  IPM
  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.


Download TeX format
back to top
Clients Logo
Clients Logo
Clients Logo
Clients Logo
Clients Logo
Clients Logo
Clients Logo
Clients Logo
scroll left or right