Molecular docking and MD: mimicking the real biological process

Sharma, Varruchi; Panwar, Anil; Gupta, Girish Kumar; Sharma, Anil Kumar

doi:10.1515/psr-2018-0164

Cited by 5 publications

(6 citation statements)

References 16 publications

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“…22 Therefore, the molecular docking of Silybin with the target protein was carried out using the Lamarckian Genetic algorithm and Local Search default parameters. 24 Developed ligands displayed significant binding as evident from the Gibbs free energy values having lower RMSD values in comparison to the original conformation. Moreover, IC50 values (i.e.…”

Section: Resultsmentioning

confidence: 99%

“…22 Molecular dynamics (MD) simulations are an effective approach in molecular docking for virtual screening of target-ligand binding ability prediction. 23,24 Silybin was molecularly docked with SARS-CoV-2 Omicron spike glycoprotein in the current investigation. The objective of the study was to discover Silybin as a potent natural compound that targets omicron spike protein to hinder its interaction with the cellular receptor of the host.…”

Section: Introductionmentioning

confidence: 96%

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Computational Docking Study of the Phytochemical Constituent, Silybin (Silybum marianum) against SARS-CoV-2 Omicron Variant Spike Glycoprotein: An In-silico Approach

Bansal¹,

Sharma²,

Panwar³

et al. 2023

J. Pure Appl. Microbiol.

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SARS-CoV-2 is continually evolving with the emergence of new variants with increased viral pathogenicity. The emergence of heavily mutated Omicron (B.1.1.529) with spike protein mutations are known to mediate its higher transmissibility and immune escape that has brought newer challenges for global public health to contain SARS-CoV-2 infection. One has to come up with a therapeutic strategy against the virus so as to effectively contain the infection and spread. Natural phytochemicals are being considered a significant source of bioactive compounds possessing an antiviral therapeutic potential. Being a promising anticancer and chemo-preventive agent, Silybin holds a significant potential to be used as a therapeutic. In the present study, molecular docking of Silybin with Omicron spike protein (7QNW) was carried out. Molecular docking results showed greater stability of Silybin in the active site of the Omicron spike protein with suitable binding mode of interactions. The study reveals that Silybin has the potential to block the host ACE2 receptor-viral spike protein binding; thereby inhibiting the viral entry to human cells. Therefore, Silybin may be further developed as a medication with the ability to effectively combat SARS-CoV-2 Omicron.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Computational Docking Study of the Phytochemical Constituent, Silybin (Silybum marianum) against SARS-CoV-2 Omicron Variant Spike Glycoprotein: An In-silico Approach

Bansal¹,

Sharma²,

Panwar³

et al. 2023

J. Pure Appl. Microbiol.

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“…12 Advancements in the structural study and the development of cutting-edge computer technology with ever-increasing computational power have opened the possibility of performing structure-based computational analysis. 13,14 MD simulations have been a popular method for understanding the dynamics of biomolecules at a molecular level by extensive exploration of phase space. 13 Such studies have boosted knowledge of the molecular mechanism of CRISPR/Cas9 in terms of structures, thermodynamics, and kinetics and have served as an excellent complement to experimental studies.…”

Section: Introductionmentioning

confidence: 99%

Insights into the Mechanism of CRISPR/Cas9-Based Genome Editing from Molecular Dynamics Simulations

Bhattacharya

Satpati

2022

ACS Omega

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The CRISPR/Cas9 system is a popular genome-editing tool with immense therapeutic potential. It is a simple two-component system (Cas9 protein and RNA) that recognizes the DNA sequence on the basis of RNA:DNA complementarity, and the Cas9 protein catalyzes the double-stranded break in the DNA. In the past decade, near-atomic resolution structures at various stages of the CRISPR/Cas9 DNA editing pathway have been reported along with numerous experimental and computational studies. Such studies have boosted knowledge of the genome-editing mechanism. Despite such advancements, the application of CRISPR/Cas9 in therapeutics is still limited, primarily due to off-target effects. Several studies aim at engineering high-fidelity Cas9 to minimize the off-target effects. Molecular Dynamics (MD) simulations have been an excellent complement to the experimental studies for investigating the mechanism of CRISPR/Cas9 editing in terms of structure, thermodynamics, and kinetics. MD-based studies have uncovered several important molecular aspects of Cas9, such as nucleotide binding, catalytic mechanism, and off-target effects. In this Review, the contribution of MD simulation to understand the CRISPR/Cas9 mechanism has been discussed, preceded by an overview of the history, mechanism, and structural aspects of the CRISPR/Cas9 system. These studies are important for the rational design of highly specific Cas9 and will also be extremely promising for achieving more accurate genome editing in the future.

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“…It has been observed that PTEN emerges as a suppressor of breast cancer growth by down-regulation of PI3K which results in cell death and arrest of the G1 phase of the cell cycle. Protein structure shows a phosphatase domain that contains 1-185 residues and a C2 domain having residues 186-351 both essential for tumor suppressor function (Sharma et al 2022c). The phoshatase domain contains the tyrosine phosphatase signature motif (H123CKAGKGR130), which forms a loop (P-loop) with the active site pocket.…”

Section: Introductionmentioning

confidence: 99%

In-silico designing of a potent ligand molecule against PTEN (Phosphatase and tensin homolog) implicated in Breast Cancer

Raghav

Sharma²,

Gupta

et al. 2022

J Exp Bio & Ag Sci

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Breast cancer has been attributed to be the second most common malignancy in females worldwide after skin cancer associated with a significantly high mortality rate. Tumor suppressor genes have an indispensable role in maintaining genomic integrity as well as cell cycle regulation. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is one of the most frequently mutated human tumor suppressor genes, implicated in cell growth, survival, and suppressing tumor formation. As the tumor progresses to more advanced stages, genetic alterations tend to increase one such alteration is the mutation of the PTEN gene which is linked to programmed cell death and maintenance of cell cycle regulation. There is a syndrome known as Cowden syndrome associated with a high risk of breast cancer which is a result of an outcome of germline mutations in the PTEN gene. Loss of PTEN activity, either at the protein or genomic level, has been related to many primary and metastatic malignancies including breast cancer. This study focuses on developing a potential bioavailable ligand inhibitory molecule for PTEN, using a computer-aided drug design approach (CADD). A library of developed ligands consisting of 50 potential molecules was screened to find a potential candidate to be used for second generation drug development. Among them, LIG28 was adjudged as the most effective and potential PTEN inhibitor given its maximum binding affinity of ΔG -5.96Kcal/mole with a lower RMSD value. Carmer’s Rule of toxicity further revealed the compatibility and non-toxicity of the molecule. These observations underscore the importance of PTEN as a target in the development of tumorigenesis and the prognosis of breast cancer.

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Molecular docking and MD: mimicking the real biological process

Cited by 5 publications

References 16 publications

Computational Docking Study of the Phytochemical Constituent, Silybin (Silybum marianum) against SARS-CoV-2 Omicron Variant Spike Glycoprotein: An In-silico Approach

Computational Docking Study of the Phytochemical Constituent, Silybin (Silybum marianum) against SARS-CoV-2 Omicron Variant Spike Glycoprotein: An In-silico Approach

Insights into the Mechanism of CRISPR/Cas9-Based Genome Editing from Molecular Dynamics Simulations

In-silico designing of a potent ligand molecule against PTEN (Phosphatase and tensin homolog) implicated in Breast Cancer

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