Introductory Chapter: Molecular Docking and Molecular Dynamics Techniques to Achieve Rational Drug Design

Stefaniu, Amalia

doi:10.5772/intechopen.84200

Cited by 10 publications

(10 citation statements)

References 24 publications

(22 reference statements)

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“…Molecular dynamics techniques help characterize various conformations and molecular interactions, allowing for the search of suitable compounds for specific biochemical purposes and reducing the consumption of chemical reagents and time 28 . Molecular dynamics simulation is a widely used approach for understanding complex systems on the atomistic scale, with applications in physics, chemistry, engineering, life, and medical science.…”

Section: Molecularmentioning

confidence: 99%

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2024

IJPSR

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Background: NCp7 is a nucleocapsid protein of HIV-1, a retrovirus causing AIDS in human beings. It is a small protein of 72 amino acids that plays an important role in being a chaperone protein involved in viral development. HIV has shown resistance to drugs engineered to treat its infections. Objectives: In this study, a Structure-Activity Relationship analysis of two distinct derivatives based on point pharmacophore was carried out to obtain an NCp7 inhibitor of better performance. Materials and Methods: A Pharmacophore and 3D-QSAR modeling of Pyridinioalkanoyl thioesters and Benzamide-based thiolcarbamates derivatives was performed. Results: A four-point hypothesis of HHRR pharmacophoric feature was determined. A 3D-QSAR model was built which was validated through regression analysis. Molecular docking often lead compounds showed that the compound ZINC65398698 possesses a higher affinity towards NCp7 protein and binds well whereas other leads possessed only moderate binding affinity. The ADME/T prediction of all the ten lead compounds showed accepted values of biophysical properties. As ZINC65398698 showed higher binding affinity, a molecular dynamics simulation was performed to determine the stability of the protein-ligand system and to study the atomistic detail of protein residue behavior after forming a complex with the ligand. The RMSD and RMSF analysis showed that the complex is highly stable throughout the production run. So the complex can be more stable within the same environment and act as potential inhibitors was determined in this procedure. Conclusions: The suggested Ligand can be then subjected to a model study after the synthesizing procedure.

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Section: Molecularmentioning

confidence: 99%

Untitled

2024

IJPSR

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“…Currently, theoretical studies such as quantum chemical calculations, molecular docking (MDock), and molecular dynamics (MD) simulations play a crucial role in rational drug design [19]. Density functional theory (DFT) has been employed to study enzyme-inhibitor interactions in medicinal chemistry and drug design [20].…”

Section: Introductionmentioning

confidence: 99%

“…MDock is the most popular computational method for drug design as it predicts the preferred orientation of a small molecule in relation to a macromolecule when they bind to form a complex [21]. This method is often complemented by molecular dynamics (MD) simulations, which explore binding pathways of active molecules in solution to aid in the selection of successful candidates [19]. Several analyses employing MD have reported replacement sugars in insulin resistance [22] and the determination of binding mechanisms of glucoamylase inhibitors through an integrated modelling study combining MD simulations and binding free energy calculations [23], as well as MD analysis of α-amylases and intestinal glucosidases using ACA and miglitol [24].…”

Section: Introductionmentioning

confidence: 99%

Theoretical Studies for the Discovery of Potential Sucrase-Isomaltase Inhibitors from Maize Silk Phytochemicals: An Approach to Treatment of Type 2 Diabetes

Landeros-Martínez,

Campos-Almazán,

Sánchez-Bojorge

et al. 2023

Molecules

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A theoretical analysis of the potential inhibition of human sucrase-isomaltase (SI) by flavonoids was carried out with the aim of identifying potential candidates for an alternative treatment of type 2 diabetes. Two compounds from maize silks, maysin and luteolin, were selected to be studied with the structure-based density functional theory (DFT), molecular docking (MDock), and molecular dynamics (MD) approaches. The docking score and MD simulations suggested that the compounds maysin and luteolin presented higher binding affinities in N-terminal sucrase-isomaltase (NtSI) than in C-terminal sucrase-isomaltase (CtSI). The reactivity parameters, such as chemical hardness (η) and chemical potential (µ), of the ligands, as well as of the active site amino acids of the NtSI, were calculated by the meta-GGA M06 functional in combination with the 6-31G(d) basis set. The lower value of chemical hardness calculated for the maysin molecule indicated that this might interact more easily with the active site of NtSI, in comparison with the values of the acarbose and luteolin structures. Additionally, a possible oxidative process was proposed through the quantum chemical calculations of the electronic charge transfer values (∆N) between the active site amino acids of the NtSI and the ligands. In addition, maysin displayed a higher ability to generate more oxidative damage in the NtSI active site. Our results suggest that maysin and luteolin can be used to develop novel α-glucosidase inhibitors via NtSI inhibition.

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“…They study its physico-chemical properties and molecular features, its behavior under various conditions and interactions with biological targets. Often, such screening research is accompanied by computational and predictive models, such as molecular docking and molecular mechanic simulations studies [1,2], conducting to lead discovery and optimization.…”

Section: Introductionmentioning

confidence: 99%

Virtual Screening of Compounds by Chemoinformatics Tools in the Chemistry Labs

Stefaniu

Pîrvu

Ungureanu

et al. 2020

The Virtual Eurachem Workshop 2020—“Quality Assurance for Analytical Laboratories in the University Curricu

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Virtual screening of compound libraries for property predictions has various applications such as: prediction of oxido-reduction potentials in view of molecular recognition, drug-likeness assessment, and design of new potential therapeutic agents, quantitative structure-property and activity relationships (QSPR/QSAR) modeling to design new structures and property predictions. Available free online platforms or specialized software provide us with vital help to design, characterize and evaluate molecular features and descriptors for imaginary systems or newly synthesized ones, to establish their potential for new applications by controlling and modeling their chemical/ biochemical behavior and properties. Predictions allow us to reduce the time spent, the cost of reagents or elaborate and costly assays, and provide us enlarged and complex perspectives.

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Introductory Chapter: Molecular Docking and Molecular Dynamics Techniques to Achieve Rational Drug Design

Cited by 10 publications

References 24 publications

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Untitled

Theoretical Studies for the Discovery of Potential Sucrase-Isomaltase Inhibitors from Maize Silk Phytochemicals: An Approach to Treatment of Type 2 Diabetes

Virtual Screening of Compounds by Chemoinformatics Tools in the Chemistry Labs

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