Prediction of Inhibition Activity of BET Bromodomain Inhibitors using Grid Search-Based Extreme Learning Machine and Molecular Docking

Abstract

Background: Inhibition activity of the epigenetic readers such as bromodomain and extra-C terminal domain protein family is of high significance in many therapeutic applications due to their ability to regulate gene expression as well as the chromatin structure by binding to acetylysine residues. Objectives: In order to effectively and quickly determine the inhibition activity of these compounds for the desired therapeutic application, this work presents a grid search-based extreme learning machine computational intelligence method through which the inhibition activity of forty different compounds of substituted 4-phenylisoquinolinones was determined. Methods: The prediction and generalization capacity of the developed model were assessed using four different error metrics including root mean square error, mean absolute error, mean absolute percentage deviation and correlation coefficient between the measured values and predicted activities. The lead compound (37), together with kinase inhibitor, LY294002 and a bromodomain and extra-C terminal inhibitor, CPI-0610 were docked with a bromodomain-containing protein 4 bromodomain 1, 6P05. Results: The developed model performed better than the existing model with percentage improvement of 44.48%, 35.08%, 20.44% and 1.23% on the basis of mean absolute percentage deviation, mean absolute error, root mean square error and correlation coefficient, respectively. The lead compound has a better binding score than LY294002 and CPI-0610. Conclusion: Implementation of the developed model would be of immense guide in searching for anti-inflammatory as well as anticancer agents for effective therapeutic application.

Molecular Dynamics and Docking Investigation of Flavonol Aglycones against Sulfonylurea Receptor 1 (SUR1) for Anti–diabetic Drug Design

“…mol −1 when compared to the other ligands. Based on this result it is evident why this ligand has been reported to be a potent inhibitor of 6PZA [7–8] . The flavonols have varying extents of binding.…”

“…Based on this result it is evident why this ligand has been reported to be a potent inhibitor of 6PZA. [7][8] The flavonols have varying extents of binding. Azaleatin, Morin and Pachypodol have binding energies closest to that of GBC (a difference of less than 20 kcal .…”

Green synthesis, Single‐Crystal X‐RD, Hirshfeld Analysis and Anti‐Covid‐19 Molecular Docking Investigation of Symmetrical Azines

“…Therefore, there is a constant need for new medications that can safely and efficiently combat SARS‐CoV‐2. Drug design and discovery have benefited from the use of molecular docking to determine how molecules (or ligands) interact with receptors [28–34] …”

“…Drug design and discovery have benefited from the use of molecular docking to determine how molecules (or ligands) interact with receptors. [28][29][30][31][32][33][34] As a result, In this study we reports the synthesis, characterisation and DFT calculations on the structural properties of the symmetrical azine (VAHD and VNHD).…”

Synthesis, spectroscopic, topological, hirshfeld surface analysis, and anti-covid-19 molecular docking investigation of isopropyl 1-benzoyl-4-(benzoyloxy)-2,6-diphenyl-1,2,5,6-tetrahydropyridine-3-carboxylate

“…Density Functional Theory (DFT) has been used solely and/or in conjunction with experimental methods for understanding the bonding and structural properties, characterization and applications of molecules 46 , 47 , 48 , 49 , 50 . Molecular docking helps to ascertain the interaction of molecules (ligands) with receptors and has been a useful technique in drug design and discovery 51 , 52 , 53 , 54 .…”