Evaluation of drug–human serum albumin binding interactions with support vector machine aided online automated docking
Open Access
- 18 May 2011
- journal article
- research article
- Published by Oxford University Press (OUP) in Bioinformatics
- Vol. 27 (13), 1806-1813
- https://doi.org/10.1093/bioinformatics/btr284
Abstract
Motivation: Human serum albumin (HSA), the most abundant plasma protein is well known for its extraordinary binding capacity for both endogenous and exogenous substances, including a wide range of drugs. Interaction with the two principal binding sites of HSA in subdomain IIA (site 1) and in subdomain IIIA (site 2) controls the free, active concentration of a drug, provides a reservoir for a long duration of action and ultimately affects the ADME (absorption, distribution, metabolism, and excretion) profile. Due to the continuous demand to investigate HSA binding properties of novel drugs, drug candidates and drug-like compounds, a support vector machine (SVM) model was developed that efficiently predicts albumin binding. Our SVM model was integrated to a free, web-based prediction platform (http://albumin.althotas.com). Automated molecular docking calculations for prediction of complex geometry are also integrated into the web service. The platform enables the users (i) to predict if albumin binds the query ligand, (ii) to determine the probable ligand binding site (site 1 or site 2), (iii) to select the albumin X-ray structure which is complexed with the most similar ligand and (iv) to calculate complex geometry using molecular docking calculations. Our SVM model and the potential offered by the combined use of in silico calculation methods and experimental binding data is illustrated. Contact:eszter.hazai@virtuadrug.com Supplementary information: Supplementary data are available at Bioinformatics online.This publication has 35 references indexed in Scilit:
- A combined spectroscopic and crystallographic approach to probing drug–human serum albumin interactionsBioorganic & Medicinal Chemistry, 2010
- Application of the PM6 semi-empirical method to modeling proteins enhances docking accuracy of AutoDockJournal of Cheminformatics, 2009
- Probable Interaction Between Warfarin and TorsemideAnnals of Pharmacotherapy, 2008
- In silico prediction of drug‐binding strengths to human serum albuminMedicinal Research Reviews, 2003
- Plasma albumin as a fatty acid carrierAdvances in Molecular and Cell Biology, 2003
- Cheminformatic Models To Predict Binding Affinities to Human Serum AlbuminJournal of Medicinal Chemistry, 2001
- Binding of the General Anesthetics Propofol and Halothane to Human Serum AlbuminOnline Journal of Public Health Informatics, 2000
- The Effect of Co-administered Drugs on Oxaprozin Binding to Human Serum AlbuminJournal of Pharmacy and Pharmacology, 1995
- Structure of Serum AlbuminAdvances in protein chemistry, 1994
- Diclofenac binding to albumin and lipoproteins in human serumBiochemical Pharmacology, 1985