Evaluation of drug-human serum albumin binding interactions with support vector machine aided online automated docking

F. Zsila, Zsolt Bikadi, David Malik, Peter Hari, Imre Pechan, Attila Berces, Eszter Hazai

Research output: Contribution to journalArticle

72 Citations (Scopus)

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.

Original languageEnglish
Article numberbtr284
Pages (from-to)1806-1813
Number of pages8
JournalBioinformatics
Volume27
Issue number13
DOIs
Publication statusPublished - Jul 2011

Fingerprint

Drug Evaluation
Docking
Serum Albumin
Support vector machines
Support Vector Machine
Drugs
Ligands
Binding sites
Evaluation
Albumins
Interaction
Pharmaceutical Preparations
Molecular Docking
Geometry
Complex Geometry
Metabolism
Web services
Binding Sites
Proteins
Plasmas

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Computational Theory and Mathematics
  • Computer Science Applications
  • Computational Mathematics
  • Statistics and Probability
  • Medicine(all)

Cite this

Evaluation of drug-human serum albumin binding interactions with support vector machine aided online automated docking. / Zsila, F.; Bikadi, Zsolt; Malik, David; Hari, Peter; Pechan, Imre; Berces, Attila; Hazai, Eszter.

In: Bioinformatics, Vol. 27, No. 13, btr284, 07.2011, p. 1806-1813.

Research output: Contribution to journalArticle

Zsila, F. ; Bikadi, Zsolt ; Malik, David ; Hari, Peter ; Pechan, Imre ; Berces, Attila ; Hazai, Eszter. / Evaluation of drug-human serum albumin binding interactions with support vector machine aided online automated docking. In: Bioinformatics. 2011 ; Vol. 27, No. 13. pp. 1806-1813.
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