Insights into the application of polyhydroxyalkanoates derivatives from the combination of experimental and simulation approaches

González‐Torres, Maykel; Villarreal-Ramírez, Eduardo; Moyaho-Bernal, María de los Ángeles; Álvarez, María Inés Fernández; González‐Valdez, José; Uribe, Janet Alejandra Gutiérrez; Leyva-Gómez, Gerardo; Cortez, J. R. Cerna

doi:10.1016/j.molstruc.2018.08.007

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…To address the stability of docked ligand into the active site of target protein, next, we carried out the molecular dynamic (MD) simulations for 10 ns using GROMACS 2020.1 [ 40 , 41 ] for the selected hits from results obtained through docking followed by manual analysis. However, MD run of ≤ 10 ns has been regarded as the more suitable and satisfactory for preliminary in silico studies as evident in scientific literatures [42] , [43] , [44] , [45] , [46] , [47] . The time-dependent stability of the ligand in the active site was studied using statistical tools such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (RoG), solvent accessible surface area (SASA) and hydrogen bonds (HB).…”

Section: Resultsmentioning

confidence: 99%

In search of RdRp and Mpro inhibitors against SARS CoV-2: Molecular docking, molecular dynamic simulations and ADMET analysis

Gajjar

Dhameliya

Shah

2021

Journal of Molecular Structure

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Corona Virus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome coronavirus (SARS CoV-2) has been declared a worldwide pandemic by WHO recently. The complete understanding of the complex genomic structure of SARS CoV-2 has enabled the use of computational tools in search of SARS CoV-2 inhibitors against the multiple proteins responsible for its entry and multiplication in human cells. With this endeavor, 177 natural, anti-viral chemical entities and their derivatives, selected through the critical analysis of the literatures, were studied using pharmacophore screening followed by molecular docking against RNA dependent RNA polymerase and main protease. The identified hits have been subjected to molecular dynamic simulations to study the stability of ligand-protein complexes followed by ADMET analysis and Lipinski filters to confirm their drug likeliness. It has led to an important start point in the drug discovery and development of therapeutic agents against SARS CoV-2.

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Section: Resultsmentioning

confidence: 99%

In search of RdRp and Mpro inhibitors against SARS CoV-2: Molecular docking, molecular dynamic simulations and ADMET analysis

Gajjar

Dhameliya

Shah

2021

Journal of Molecular Structure

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“…To study the stability of ligand into the binding site of protein, molecular dynamics (MD) simulations provide the better understanding of ligand through several statistical parameters [ 48 , 49 ]. Several scientific literatures support the reliability and satisfactory stability for the MD run (≤ 10 ns) through in silico endeavor [50] , [51] , [52] , [53] , [54] , [55] . In a similar line of approach, the hit complexes obtained from the evaluation of ADMET and drug-likeliness properties, were subjected for MD simulations using GROMACS 2020.1 to assess the stability of the stability of the ligands ( 2 - 3 ) in the active site of docked complex at various time points up to 10 ns [ 56 , 57 ].…”

Section: Resultsmentioning

confidence: 88%

In search of SARS CoV-2 replication inhibitors: Virtual screening, molecular dynamics simulations and ADMET analysis

Nagar

Gajjar

Dhameliya

2021

Journal of Molecular Structure

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Severe acute respiratory syndrome has relapsed recently as novel coronavirus causing a life threat to the entire world in the absence of an effective therapy. To hamper the replication of the deadly SARS CoV-2 inside the host cells, systematic in silico virtual screening of total 267,324 ligands from Asinex EliteSynergy and BioDesign libraries has been performed using AutoDock Vina against RdRp. The molecular modeling studies revealed the identification of twenty-one macrocyclic hits ( 2 - 22 ) with better binding energy than remdesivir ( 1 ), marketed SARS CoV-2 inhibitor. Further, the analysis using rules for drug-likeness and their ADMET profile revealed the candidature of these hits due to superior oral bioavailability and druggability. Further, the MD simulation studies of top two hits ( 2 and 3 ) performed using GROMACS 2020.1 for 10 ns revealed their stability into the docked complexes. These results provide an important breakthrough in the design of macrocyclic hits as SARS CoV-2 RNA replicase inhibitor.

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“…With a view of exploring the stability of ligand into the active site of protein through various statistical parameters, molecular dynamics (MD) simulations[ 74 , 75 ] were carried out for 10 ns. [ 76 , 77 , 78 , 79 , 80 , 81 ] The hit complexes obtained from docking analysis were incorporated for MD simulations at various time points up to 10 ns using GROMACS 2020.1. [ 82 , 83 ] MD simulation was performed for complexes of Mpro with clemastanin B, spike glycoprotein with clemastanin B, Nsp 10/16 with secoisolariciresinol, PLpro with clemastanin B/savinin, and RdRp with clemastanin B.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

In‐silico Computational Investigations of AntiViral Lignan Derivatives as Potent Inhibitors of SARS CoV‐2

Sureja¹,

Shah²,

Gajjar³

et al. 2022

ChemistrySelect

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Due to alarming outbreak of pandemic COVID‐19 in recent times, there is a strong need to discover and identify new antiviral agents acting against SARS CoV‐2. Among natural products, lignan derivatives have been found effective against several viral strains including SARS CoV‐2. Total of twenty‐seven reported antiviral lignan derivatives of plant origin have been selected for computational studies to identify the potent inhibitors of SARS CoV‐2. Molecular docking study has been carried out in order to predict and describe molecular interaction between active site of enzyme and lignan derivatives. Out of identified hits, clemastatin B and erythro‐strebluslignanol G demonstrated stronger binding and high affinity with all selected proteins. Molecular dynamics simulation studies of clemastin B and savinin against promising targets of SARS CoV‐2 have revealed their inhibitory potential against SARS CoV‐2. In fine, in‐silico computational studies have provided initial breakthrough in design and discovery of potential SARS CoV‐2 inhibitors.

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Insights into the application of polyhydroxyalkanoates derivatives from the combination of experimental and simulation approaches

Cited by 8 publications

References 32 publications

In search of RdRp and Mpro inhibitors against SARS CoV-2: Molecular docking, molecular dynamic simulations and ADMET analysis

In search of RdRp and Mpro inhibitors against SARS CoV-2: Molecular docking, molecular dynamic simulations and ADMET analysis

In search of SARS CoV-2 replication inhibitors: Virtual screening, molecular dynamics simulations and ADMET analysis

In‐silico Computational Investigations of AntiViral Lignan Derivatives as Potent Inhibitors of SARS CoV‐2

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