Quantum-Chemical Quasi-Docking for Molecular Dynamics Calculations

Сулимов, А. В.; Kutov, Danil; Ilin, İvan; Сулимов, В. Б.

doi:10.3390/nano12020274

Cited by 7 publications

(3 citation statements)

References 35 publications

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“…The MOPAC program and the PM7 method were chosen for these calculations because MOPAC could process protein–ligand complexes with sufficient speed due to the use of the localized molecular orbital method implemented in the MOZYME module, and PM7 described dispersion interactions as well as hydrogen and halogen bonds with an accuracy approaching that obtained by DFT methods. The combination of PM7/COSMO gave a strong correlation coefficient (0.74) between the calculated and experimentally measured protein–ligand binding enthalpy [ 77 , 78 ].…”

Section: Methodsmentioning

confidence: 99%

New Chemicals Suppressing SARS-CoV-2 Replication in Cell Culture

et al. 2022

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Candidates to being inhibitors of the main protease (Mpro) of SARS-CoV-2 were selected from the database of Voronezh State University using molecular modeling. The database contained approximately 19,000 compounds represented by more than 41,000 ligand conformers. These ligands were docked into Mpro using the SOL docking program. For one thousand ligands with best values of the SOL score, the protein–ligand binding enthalpy was calculated by the PM7 quantum-chemical method with the COSMO solvent model. Using the SOL score and the calculated protein–ligand binding enthalpies, eighteen compounds were selected for the experiments. Several of these inhibitors suppressed the replication of the coronavirus in cell culture, and we used the best three among them in the search for chemical analogs. Selection among analogs using the same procedure followed by experiments led to identification of seven inhibitors of the SARS-CoV-2 replication in cell culture with EC50 values at the micromolar level. The identified inhibitors belong to three chemical classes. The three inhibitors, 4,4-dimethyldithioquinoline derivatives, inhibit SARS-CoV-2 replication in Vero E6 cell culture just as effectively as the best published non-covalent inhibitors, and show low cytotoxicity. These results open up a possibility to develop antiviral drugs against the SARS-CoV-2 coronavirus.

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Section: Methodsmentioning

confidence: 99%

New Chemicals Suppressing SARS-CoV-2 Replication in Cell Culture

et al. 2022

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“…This makes it particularly suitable for studying protein-ligand interactions, where the size and complexity of the system can otherwise limit the applicability of quantum mechanical methods. The MOZYME method is implement in the MOPAC software [73][74][75][76][77].…”

Section: Mozymementioning

confidence: 99%

Molecular Docking in Drug Discovery: Techniques, Applications, and Advancements

Aguiar,

Camps

2024

Preprint

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Objective: The primary objective of this study is to conduct a comprehensive review of the significance of molecular docking in the field of drug discovery. This includes an examination of the various approaches and methods used in molecular docking, as well as an exploration of the techniques used for interpreting and validating docking results. Methods: To gather relevant data, a systematic search was conducted using Web of Science, PubMed, and Google Scholar. The search focused on articles related to molecular docking methodologies and their applications in drug discovery. Additionally, alternative techniques that can be used for more precise simulations of ligand-protein interactions were also considered. Results: Molecular docking has proven to be an incredibly rich and valuable process in the field of drug discovery. Its flexibility allows for the incorporation of advanced computational techniques, thereby enhancing the reliability and efficiency of drug discovery processes. The results of the study highlight the significant strides made in the field of molecular docking, demonstrating its potential to revolutionize drug discovery. Conclusions: Molecular docking continues to evolve, with new advancements being made regularly. Despite the challenges faced, these advancements have significantly contributed to the enhancement of molecular docking, solidifying its position as a crucial tool in the field of drug discovery.

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“…The clustering histogram shows the number of binding conformations at different binding energies. A number of clusters with high population indicates, as a rule, that docking has been successfully performed [53,54].…”

Section: Visualization Between Rms Compounds Of Pms and Dna Gyrase IImentioning

confidence: 99%

In Silico Activity Prediction and Docking Studies of the Binding Mechanisms of Levofloxacin Structure Derivatives to Active Receptor Sites of Bacterial Type IIA Topoisomerases

Uspenskaya,

Sukhanova,

Kuzmina

et al. 2023

Sci. Pharm.

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The need for new antimicrobial agents (AntAg) is driven by the persistent antibiotic resistance in microorganisms, as well as the increasing frequency of pandemics. Due to the deficiency of AntAg, research aimed at developing speedy approaches to find new drug candidates is relevant. This study aims to conduct an in silico study of the biological activity spectrum as well as the molecular binding mechanisms of four structurally different forms of levofloxacin (Lvf) with bacterial topoisomerases targets of type IIA (DNA gyrase and topoisomerase IV) to enable the development of drugs with an improved characterization of the safety profile. To achieve this goal, a number of software products were used, such as ChemicPen v. 2.6, PyMol 2.5, Avogadro 1.2.0, PASS, AutoDockTools 1.5.7 with the new generation software Autodock Vina. These software products are the first to be made available for visualization of clusters with determination of ligand-receptor pair binding affinity, as well as clustering coordinates and proposed mechanisms of action. One of the real structures of Lvf, a decarboxylated derivative, was obtained with tribochemical (TrbCh) exposure. The action spectrum of molecular ligands is described based on a Bayesian probability activity prediction model (PASS software Version 2.0). Predicted and real (PMS and RMS) molecular structures of Lvf, with decreasing levels of structural complexity, were translated into descriptors via Wiener (W), Balaban (Vs), Detour (Ip), and Electropy € indices. The 2D «structure-activity» diagrams were used to differentiate closely related structures of levofloxacin. PMS and RMS were visualized as 3D models of the ligand-receptor complexes. The contact regions of RMS and PMS with key amino acid residues—SER-79, DT-15, DG-1, DA-1—were demonstrated. The intra- and inter-molecular binding sites, data on free energy (affinity values, kcal/mol), the binding constant Kb (M−1), and the number of clusters are presented. The research results obtained from the presented in silico approach to explore the spectrum of action find quantitative “structure-activity” correlations, and predict molecular mechanisms may be of applied interest for directed drug discovery.

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Quantum-Chemical Quasi-Docking for Molecular Dynamics Calculations

Cited by 7 publications

References 35 publications

New Chemicals Suppressing SARS-CoV-2 Replication in Cell Culture

New Chemicals Suppressing SARS-CoV-2 Replication in Cell Culture

Molecular Docking in Drug Discovery: Techniques, Applications, and Advancements

In Silico Activity Prediction and Docking Studies of the Binding Mechanisms of Levofloxacin Structure Derivatives to Active Receptor Sites of Bacterial Type IIA Topoisomerases

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