Knowledge-based annotation of small molecule binding sites in proteins

Background: The study of protein-small molecule interactions is vital for understanding protein function and for practical applications in drug discovery. To benefit from the rapidly increasing structural data, it is essential to improve the tools that enable large scale binding site prediction with greater emphasis on their biological validity. Results: We have developed a new method for the annotation of protein-small molecule binding sites, using inference by homology, which allows us to extend annotation onto protein sequences without experimental data available. To ensure biological relevance of binding sites, our method clusters similar binding sites found in homologous protein structures based on their sequence and structure conservation. Binding sites which appear evolutionarily conserved among non-redundant sets of homologous proteins are given higher priority. After binding sites are clustered, position specific score matrices (PSSMs) are constructed from the corresponding b...

• Type: Journal
• Year: 2010
• Where: BMCBI
• Authors: Ratna R. Thangudu, Manoj Tyagi, Benjamin A. Shoemaker, Stephen H. Bryant, Anna R. Panchenko, Thomas Madej
• Keywords: Binding Sites, BMCBI 2010, Protein-small Molecule, Small Molecules