Insights into amyotrophic lateral sclerosis linked Pro525Arg mutation in the fused in sarcoma protein through in silico analysis and molecular dynamics simulation

2020 ◽  
pp. 1-14 ◽  
Author(s):  
Sompriya Chatterjee ◽  
Abbas Salimi ◽  
Jin Yong Lee
Keyword(s):  
Molecular Dynamics ◽  
Amyotrophic Lateral Sclerosis ◽  
Molecular Dynamics Simulation ◽  
In Silico ◽  
In Silico Analysis ◽  
Dynamics Simulation ◽  
Fused In Sarcoma ◽  
Silico Analysis ◽  
Lateral Sclerosis

SOD1 in amyotrophic lateral sclerosis development – in silico analysis and molecular dynamics of A4F and A4V variants

2019 ◽  
Vol 120 (10) ◽  
pp. 17822-17830 ◽  
Author(s):  
Aloma Nogueira Rebello Da Silva ◽  
Gabriel Rodrigues Coutinho Pereira ◽  
Lorena Giannini Alves Moreira ◽  
Catielly Ferreira Rocha ◽  
Joelma Freire Mesquita
Keyword(s):  
Molecular Dynamics ◽  
Amyotrophic Lateral Sclerosis ◽  
In Silico ◽  
In Silico Analysis ◽  
Silico Analysis ◽  
Lateral Sclerosis

In vitro evaluation and molecular dynamics, DFT guided investigation of antimalarial activity of ethnomedicinally used Coptis teeta Wall

2021 ◽  
Vol 24 ◽  
Author(s):  
Ashis Kumar Goswami ◽  
Hemanta Kumar Sharma ◽  
Neelutpal Gogoi ◽  
Ankita Kashyap ◽  
Bhaskar Jyoti Gogoi
Keyword(s):  
Molecular Dynamics ◽  
In Silico ◽  
Density Functional ◽  
Antimalarial Activity ◽  
In Silico Analysis ◽  
Dynamics Simulation ◽  
Discovery Studio ◽  
North East ◽  
Silico Analysis

Background: Malaria is caused by different species of Plasmodium; among which P. falciparum is the most severe. Coptis teeta is an ethnomedicinal plant of enormous importance for tribes of north east India. Objective: In this study, the anti malarial activity of the methanol extracts of Coptis teeta was evaluated in vitro and lead identification via in silico study. Method: On the basis of the in vitro results, in silico analysis by application of different modules of Discovery Studio 2018 was performed on multiple targets of P. falciparum taking into consideration some of the compounds reported from C. teeta. Results: The IC50 of the methanol extract of Coptis teeta 0.08 µg/ml in 3D7 strain and 0.7 µg/ml in Dd2 strain of P. falciparum. From the docking study, noroxyhydrastatine was observed to have better binding affinity in comparison to chloroquine. The binding of noroxyhydrastinine with dihydroorotate dehydrogenase was further validated by molecular dynamics simulation and was observed to be significantly stable in comparison to the co-crystal inhibitor. During simulations it was observed that noroxyhydrastinine retained the interactions, giving strong indications of its effectiveness against the P. falciparum proteins and stability in the binding pocket. From the Density-functional theory analysis, the band gap energy of noroxyhydrastinine was found to be 0.186 Ha indicating a favourable interaction. Conclusion: The in silico analysis as an addition to the in vitro results provide strong evidence of noroxyhydrastinine as an anti malarial agent.

scholarly journals In silico analysis of PFN1 related to amyotrophic lateral sclerosis

PLoS ONE ◽  
2019 ◽  
Vol 14 (6) ◽  
pp. e0215723
Author(s):  
Gabriel Rodrigues Coutinho Pereira ◽  
Giovanni Henrique Almeida Silva Tellini ◽  
Joelma Freire De Mesquita
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
In Silico ◽  
In Silico Analysis ◽  
Silico Analysis ◽  
Lateral Sclerosis

Screening of natural compounds against SOD1 as a therapeutic target for Amyotrophic lateral sclerosis

2021 ◽  
Vol 19 ◽  
Author(s):  
Sonu Pahal ◽  
Amit Chaudhary ◽  
Sangeeta Singh
Keyword(s):  
Molecular Dynamics ◽  
Amyotrophic Lateral Sclerosis ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Virtual Screening ◽  
Dynamics Simulation ◽  
Pharmacokinetic Parameters ◽  
Wild Type ◽  
Potential Inhibitors ◽  
Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is an uncommon and progressive neurological illness that predominantly includes the neurons liable for voluntary muscular activities. Starting from weakness or stiffness in muscles, this gradually exploits the strength and ability to speak, eat, move and even breathe. Its exact mechanism is still not clear, but mutations in the SOD1 gene have been reported to cause ALS, and some studies also found involvement of SOD1 overexpression in the pathogenesis of ALS. As of now, there is no remedy available for its cure. Objective: To identify the potential inhibitors for wild type 1HL5, l113T mutant, and A4V mutant of SOD1 (Superoxide Dismutase 1) protein. Methods: In this study, in silico approaches like virtual screening, molecular docking, pharmacokinetic parameters study, and molecular dynamics simulation were used to identify the best potential inhibitors against wild type and mutant SOD1 protein. Methods: In this study, in silico approaches like virtual screening, molecular docking, pharmacokinetic parameters study, and molecular dynamics simulation were used to identify the best potential inhibitors against wild type and mutant SOD1 protein. Results: On the basis of binding affinity and binding energy, the top three compounds ZINC000095486263, ZINC000095485989, and ZINC000028462577, were observed as the best compounds. In the case of 1HL5, ZINC000095486263 had the highest binding affinity with docking score -10.62 Kcal/mol, 1UXM with ZINC000095485989 had the highest docking score -12.03 Kcal/mol, and 4A7V with ZINC000028462577 was found -11.72 Kcal/mol. Further, Molecular Dynamic simulations (MDS) results showed that the ZINC000095486263, ZINC000095485989, and ZINC000095485956 compounds were formed a stable complex with 1HL5, 1UXM, and 4A7V, respectively Conclusions: : After analyzing the results, we hereby conclude that naturals compounds such as ZINC000095486263, ZINC000095485989, and ZINC000095485956 could be used as a potential inhibitor of 1HL5, 1UXM, and 4A7V, respectively, for ALS treatment and could be used as a drug. Further, In vivo/vitro study of these compounds could be a future direction in the field of drug discovery.

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