Enhancing HDAC Inhibitor Screening: Addressing Zinc Parameterization and Ligand Protonation in Docking Studies

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 850 - 850

Published: Jan. 20, 2025

Precise binding free-energy predictions for ligands targeting metalloproteins, especially zinc-containing histone deacetylase (HDAC) enzymes, require specialized computational approaches due to the unique interactions at metal-binding sites. This study evaluates a docking algorithm optimized zinc coordination determine whether it could accurately differentiate between protonated and deprotonated states of hydroxamic acid ligands, key functional group in HDAC inhibitors (HDACi). By systematically analyzing both protonation states, we sought identify which state produces poses energy estimates most closely aligned with experimental values. The was applied across 2, 4, 8, comparing ligand correlations data. results demonstrate that consistently yielded stronger data, R2 values outperforming counterparts all targets (average = 0.80 compared form where 0.67). These findings emphasize significance proper molecular studies zinc-binding particularly HDACs, suggest deprotonation enhances predictive accuracy. study’s methodology provides robust foundation improved virtual screening protocols evaluate large libraries efficiently. approach supports streamlined discovery high-affinity, HDACi, advancing therapeutic exploration metalloprotein targets. A comprehensive, step-by-step tutorial is provided facilitate thorough understanding enable reproducibility results.

Language: Английский

Twenty years in metalloprotein bioinformatics: A short history of a long journey

Journal of Inorganic Biochemistry, Journal Year: 2025, Volume and Issue: 266, P. 112854 - 112854

Published: Feb. 11, 2025

Language: Английский

β-Lactoglobulin Enhances Clay and Activated Carbon Binding and Protection Properties for Cadmium and Lead

Industrial & Engineering Chemistry Research, Journal Year: 2024, Volume and Issue: 63(37), P. 16124 - 16140

Published: Sept. 6, 2024

The removal of heavy metals from wastewater remains a challenge due to the limitations current remediation methods. This study aims develop multicomponent composites as inexpensive and environmentally friendly sorbents with enhanced capture cadmium (Cd) lead (Pb). are based on calcium montmorillonite (CM) activated carbon (AC) because their proven effectiveness for diverse toxins in environmental settings. In this study, we used combination computational experimental methods delineate that β-lactoglobulin enhances CM AC binding protection properties Cd Pb. Modeling molecular dynamics simulations investigated formation material systems formed by complex predicted capacity bind metal ions at neutral pH conditions. Our suggest attributed presence several pockets two ions. At conditions, divalent Pb shared comparable propensities all systems, former being consistently higher than latter. To validate interactions depicted simulations, ecotoxicological models (

Language: Английский