Pharmacophore-based virtual screening, molecular docking, molecular dynamics simulation, and biological evaluation for the discovery of novel BRD4 inhibitors

2017 ◽  
Vol 91 (2) ◽  
pp. 478-490 ◽  
Author(s):  
Guoyi Yan ◽  
Manzhou Hou ◽  
Jiang Luo ◽  
Chunlan Pu ◽  
Xueyan Hou ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Virtual Screening ◽  
Biological Evaluation ◽  
Dynamics Simulation

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.

scholarly journals Discovery of Potential Compounds Against SARS-COV-2 Based on 3clpro/Rdrp Dual-Target an in Silico Approach

2021 ◽  
Author(s):  
Jiaojiao Li ◽  
Lin Zhu ◽  
Zheng Qin ◽  
Zhengfu Li ◽  
Xun Gao ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Virtual Screening ◽  
Severe Acute Respiratory Syndrome ◽  
Rna Polymerase ◽  
Dynamics Simulation ◽  
Rna Dependent Rna Polymerase ◽  
Simulation Results ◽  
Dual Target

Abstract Currently, Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) lacks clinically specific drugs. In this study, the new coronavirus SARS-CoV-2 3-chymotrypsin-like protease(3CLpro)and RNA-dependent RNA polymerase(RdRp)were used as targets for virtual screening. After analysis of molecular docking and molecular dynamics simulation results, ZINC04259665,ZINC12659533 and ZINC70705490 have good docking scores,and they are stable in combination with 3CLpro/RdRp. The prediction of drug-like properties found that ZINC04259665 has good druggability and has the potential to further explore its anti-SARS-CoV-2.

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