Implication of Ab Initio, QM/MM, and molecular dynamics calculations on the prediction of the therapeutic potential of some selected HDAC inhibitors

Dushanan, Ramachandren; Weerasinghe, Samantha; Dissanayake, D. P.; Senthilinithy, Rajendram

doi:10.1080/08927022.2022.2097672

Cited by 8 publications

(4 citation statements)

References 65 publications

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“…We plan to perform these calculations in the near future. Ab initio MD calculations using quantum mechanical (QM), molecular mechanics (MM), and ONIOM (our own n-layered integrated molecular orbital and molecular mechanics) methods [47][48][49][50][51][52] are effective for calculating the medium effects.…”

Section: Remarksmentioning

confidence: 99%

Mechanism of ionic dissociation of HCl in the smallest water clusters

Tachikawa

2024

Phys. Chem. Chem. Phys.

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Section: Remarksmentioning

confidence: 99%

Mechanism of ionic dissociation of HCl in the smallest water clusters

Tachikawa

2024

Phys. Chem. Chem. Phys.

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“…In QM setting this is found by understanding the change in potential energy surface (PES) between states. This approach extends on how ligands interact with targets to understand how the PES is modified or overcome by generation or outcompeting of bonds [ 400 , 418 , 419 , 420 , 421 ]. Extending from PES alone, application analytical tools related to the properties of the wavefunction can be used to describe, modify and improve ligands.…”

Section: Qm/mm and Dft Approachesmentioning

confidence: 99%

A Guide to In Silico Drug Design

Chang

Hawkins

et al. 2022

Pharmaceutics

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The drug discovery process is a rocky path that is full of challenges, with the result that very few candidates progress from hit compound to a commercially available product, often due to factors, such as poor binding affinity, off-target effects, or physicochemical properties, such as solubility or stability. This process is further complicated by high research and development costs and time requirements. It is thus important to optimise every step of the process in order to maximise the chances of success. As a result of the recent advancements in computer power and technology, computer-aided drug design (CADD) has become an integral part of modern drug discovery to guide and accelerate the process. In this review, we present an overview of the important CADD methods and applications, such as in silico structure prediction, refinement, modelling and target validation, that are commonly used in this area.

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“…The g_dist tool was used to look into the stability of hydrogen bonds. The hydrogen bonds that exist between the ligand and the protein have an impact on the stability of the complex [47]. Fig.…”

Section: Hydrogen Bonds Analysismentioning

confidence: 99%

Exploration of Novel Mono Hydroxamic Acid Derivatives as Inhibitors for Histone Deacetylase Like Protein (HDLP) by Molecular Dynamics Studies

et al. 2022

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The acetylation modification process of histone has an essential role in the epigenetic regulation of gene expression. This process is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDACs are thought to be vital for cell function. Particularly, higher HDAC expression is frequent in various cancers, resulting in the dysregulation of several target genes involved in cell proliferation, differentiation, and survival. In this study, the inhibitory feasibility of several HDAC inhibitors was investigated, including vorinostat (SAHA), N-hydroxy-3-phenylprop-2-enamide (CPD1), N-hydroxy-3-(pyridine-4-yl)prop-2-enamide (CPD2), N-hydroxy-3-(pyridine-2-yl)prop-2-enamide (CPD3), 4-(diphenylamino)-N-(5-(hydroxyamino)-5-oxopentyl)benzamide (CPD4), 2-(6-(((6-fluoronaphthalen-2-yl)methyl)amino)-3-azabicyclo[3.1.0]hex-3-yl)-N-hydroxypirimidine-5-carboxamide (CPD5), and N-(3-aminopropyl)-N-hydroxy-2-((naphthalene-1-yloxy)methyl)oct-2-enediamide (CPD6). By examining the stability of the enzyme, positional stability of the individual amino acids, and binding energies of HDLP-inhibitor complexes, the inhibitory feasibility was assessed. The complexes of the HDLP enzyme with SAHA, CPD4, CPD5, and CPD6 had higher stability than the other studied complexes, according to the results of trajectory analysis and the Ramachandran plot. Based on the calculated MM-PBSA binding free energies, the stability of the HDLP enzyme followed this order CPD4 > CPD5 > SAHA > CPD6 > CPD2 > CPD3 > CPD1. The drugability values followed the same trend as the previous ones. Based on the obtained in silico results, CPD4, CPD5, and CPD6 were discovered to be possible lead compounds as reference inhibitors of SAHA.

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Implication of Ab Initio, QM/MM, and molecular dynamics calculations on the prediction of the therapeutic potential of some selected HDAC inhibitors

Cited by 8 publications

References 65 publications

Mechanism of ionic dissociation of HCl in the smallest water clusters

Mechanism of ionic dissociation of HCl in the smallest water clusters

A Guide to In Silico Drug Design

Exploration of Novel Mono Hydroxamic Acid Derivatives as Inhibitors for Histone Deacetylase Like Protein (HDLP) by Molecular Dynamics Studies

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