Investigation of intermolecular interactions and binding mechanism of PU139 and PU141 molecules with p300 HAT enzyme via molecular docking, molecular dynamics simulations and binding free energy analysis

Aim and Objective: Isoflavone phytoestrogens, which commonly present in natural plants, are closely related to human health. The combination of them with estrogen receptors in the body can play a more important role in the prevention and treatment of cardiovascular diseases, cancer, and menopausal diseases. This research is conducted for the wider application of isoflavone phytoestrogens in various fields. Method: In this study, molecular docking studies and molecular dynamics simulations were performed to explore the affinities and interaction between three typical isoflavone phytoestrogens and estrogen receptors (ERα and ERβ), respectively. Results and Conclusion: Molecular docking results showed that the affinity of genistein, daidzein and formononetin was different, and the ligand structures and hydrogen bonds force were the main factors affecting the binding abilities. The calculation of the binding free energy shows the stability of the complex and the contribution of various interactions to the binding free energy. The decomposition of binding free energy indicates that van der Waals interaction and electrostatic interaction promote the binding of the complex, which are in agreement with the docking studies.

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Molecular Modeling Approach to Investigate the Intercalation of Phthalates and Their Metabolites in DNA Macromolecules

Journal of Computational and Theoretical Nanoscience ◽

10.1166/jctn.2019.8110 ◽

2019 ◽

Vol 16 (2) ◽

pp. 373-380 ◽

Cited By ~ 1

Author(s):

Tatiane P. Rodrigues ◽

Jorddy N. Cruz ◽

Tiago S. Arouche ◽

Tais S. S. Pereira ◽

Wanessa A. Costa ◽

...

Keyword(s):

Molecular Dynamics ◽

Free Energy ◽

Molecular Docking ◽

Molecular Modeling ◽

Molecular Dynamics Simulations ◽

Binding Free Energy ◽

Van Der Waals ◽

Genetic Material ◽

Ligand Interaction ◽

Dynamics Simulations

Recent studies have reported that phthalates are capable of causing mutations and other changes in the genetic material. This study aimed to investigate the molecular interactions between phthalate di(2-ethylhexyl) phthalate (DEHP) and its metabolites monobutyl phthalate (MBP) and monoethyl phthalate (MEP), interacting with DNA. The research was conducted using molecular modeling techniques such as molecular docking and molecular dynamics simulations. Molecular docking revealed that the DEHP, MBP, and MEP are able to establish hydrogen interactions with various nucleotide bases. Molecular dynamics simulations revealed that these molecules interacted with the DNA, and the binding free energy results demonstrated that the DNA-ligand interaction has favorable free energy. The values for free binding energy were as follows: DNA–DEHP, –21.66 kcal/mol; DNA–MBP, –17.29 kcal/mol; and DNA–MEP, –20.13 kcal/mol. For these three systems, the contributions of van der Waals, electrostatic, and nonpolar solvation energy were favorable for the interaction. The van der Waals interactions contributed the major energy to the intercalation of the binders.

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Carbohydrate-Protein Recognition: Molecular Dynamics Simulations and Free Energy Analysis of Oligosaccharide Binding to Concanavalin A

Biophysical Journal ◽

10.1016/s0006-3495(01)75793-1 ◽

2001 ◽

Vol 81 (3) ◽

pp. 1373-1388 ◽

Cited By ~ 63

Author(s):

R.A. Bryce ◽

I.H. Hillier ◽

J.H. Naismith

Keyword(s):

Molecular Dynamics ◽

Free Energy ◽

Molecular Dynamics Simulations ◽

Concanavalin A ◽

Energy Analysis ◽

Protein Recognition ◽

Dynamics Simulations ◽

Free Energy Analysis

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Comparative molecular dynamics simulations of histone deacetylase-like protein: Binding modes and free energy analysis to hydroxamic acid inhibitors

Proteins Structure Function and Bioinformatics ◽

10.1002/prot.22047 ◽

2008 ◽

Vol 73 (1) ◽

pp. 134-149 ◽

Cited By ~ 33

Author(s):

Chunli Yan ◽

Zhilong Xiu ◽

Xiaohui Li ◽

Shenmin Li ◽

Ce Hao ◽

...

Keyword(s):

Molecular Dynamics ◽

Free Energy ◽

Protein Binding ◽

Molecular Dynamics Simulations ◽

Histone Deacetylase ◽

Hydroxamic Acid ◽

Energy Analysis ◽

Binding Modes ◽

Dynamics Simulations ◽

Free Energy Analysis

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Identification of Potential Binders of the SARS-Cov-2 Spike Protein via Molecular Docking, Dynamics Simulation and Binding Free Energy Calculation

10.26434/chemrxiv.12278588 ◽

2020 ◽

Author(s):

Dr. Chirag N. Patel ◽

Dr. Prasanth Kumar S. ◽

Dr. Himanshu A. Pandya ◽

Dr. Rakesh M. Rawal

Keyword(s):

Molecular Dynamics ◽

Free Energy ◽

Molecular Docking ◽

Molecular Dynamics Simulations ◽

Binding Free Energy ◽

Free Energy Calculations ◽

Dynamics Simulation ◽

Spike Protein ◽

Energy Calculations ◽

Dynamics Simulations

<p>The pandemic outbreak of COVID-19 virus (SARS-CoV-2) has become critical global health issue. The biophysical and structural evidence shows that SARS-CoV-2 spike protein possesses higher binding affinity towards angiotensin-converting enzyme 2 (ACE2) and hemagglutinin-acetylesterase (HE) glycoprotein receptor. Hence, it was selected as a target to generate the potential candidates for the inhibition of HE glycoprotein. The present study focuses on extensive computational approaches which contains molecular docking, ADMET prediction followed by molecular dynamics simulations and free energy calculations. Furthermore, virtual screening of NPACT compounds identified 3,4,5-Trihydroxy-1,8-bis[(2R,3R)-3,5,7-trihydroxy-3,4-dihydro-2H-chromen-2-yl]benzo[7]annulen-6-one, Silymarin, Withanolide D, Spirosolane and Oridonin were interact with high affinity. The ADMET prediction revealed pharmacokinetics and drug-likeness properties of top-ranked compounds. Molecular dynamics simulations and binding free energy calculations affirmed that these five NPACT compounds were robust HE inhibitor.</p>

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