Developing a method to identify small molecule binding sites on proteins : a case study with ATP.

• Main Author: Li, Kun Quan.
• Other Authors: School of Biological Sciences
• Format: Final Year Project
• Language: English
• Published: 2010
• Subjects: DRNTU::Science::Biological sciences::Biomathematics
• Online Access: http://hdl.handle.net/10356/40042
• Institution: Nanyang Technological University

The binding of small molecule ligands onto proteins is a key step in many cellular processes. Depending on the flexibility of ligands and proteins, binding sites can differ in terms of shape and size, allowing different interactions of the protein with ligands of different confirmation. The aim of this study is to develop a method to identify small molecule binding sites on proteins. First, a database of the different confirmations of the small molecule is created. Application of the methodology was carried out using adenosine triphosphate (ATP) in this study. A training set of 13 major clusters with different ATP confirmations and a test set of 26 proteins that were not included in the training set, were obtained. Structural superimposition was done to match common alpha carbons of residues in the binding pockets with alpha carbons of residues from the binding pockets of other proteins within the same cluster. For each cluster, a descriptor was determined by taking the average coordinates of matching alpha carbons sets. 26 test proteins were tested against each of the 13 descriptor sets. Two tests were run with cut-off values of 4Å and 6Å, obtaining accuracy of 91% and 63% respectively. Using this method, protein structures in the protein database can then be annotated for ligand binding pockets, to discover if they have the potential to bind to certain small molecules. This procedure could be a useful for the virtual screening of potential drugs against specific protein targets.