Multi-Cavity Molecular Descriptor Interconnections: Enhanced Protocol for Prediction of Serum Albumin Drug Binding

Eur J Pharm Biopharm. 2023 Nov 18:S0939-6411(23)00292-8. doi: 10.1016/j.ejpb.2023.11.003. Online ahead of print.ABSTRACTThe role of human serum albumin (HSA) in the transport of molecules predicates its involvement in the determination of drug distribution and metabolism. Optimization of ADME properties are analogous to HSA binding thus this is imperative to the drug discovery process. Currently, various in silico predictive tools exist to complement the drug discovery process, however, the prediction of possible ligand-binding sites on HSA has posed several challenges. Herein, we present a strong and deeper-than-surface case for the prediction of HSA-ligand binding sites using multi-cavity molecular descriptors by exploiting all experimentally available and crystallized HSA-bound drugs. Unlike previously proposed models found in literature, we established an in-depth correlation between the physicochemical properties of available crystallized HSA-bound drugs and different HSA binding site characteristics to precisely predict the binding sites of investigational molecules. Molecular descriptors such as the number of hydrogen bond donors (nHD), number of heteroatoms (nHet), topological polar surface area (TPSA), molecular weight (MW), and distribution coefficient (LogD) were correlated against HSA binding site characteristics, including hydrophobicity, hydrophilicity, enclosure, exposure, contact, site volume, and donor/acceptor ratio. Molecular descriptors nHD, TPSA, LogD, nH...

Source: European Journal of Pharmaceutics and Biopharmaceutics - November 20, 2023 Category: Drugs & Pharmacology Authors: Oluwole B Akawa Felix O Okunlola Mohammed Issa Alahmdi Nader E Abo-Dya Peter A Sidhom Mahmoud A A Ibrahim Mohamed F Shibl Shahzeb Khan Mahmoud E S Soliman Source Type: research