Kinome-wide interaction modelling using alignment-based and alignment-independent approaches for kinase description and linear a

Background: Protein kinases play crucial roles in cell growth, differentiation, and apoptosis. Abnormal function of protein kinases can lead to many serious diseases, such as cancer. Kinase inhibitors have potential for treatment of these diseases. However, current inhibitors interact with a broad variety of kinases and interfere with multiple vital cellular processes, which causes toxic effects. Bioinformatics approaches that can predict inhibitor-kinase interactions from the chemical properties of the inhibitors and the kinase macromolecules might aid in design of more selective therapeutic agents, that show better efficacy and lower toxicity. Results: We applied proteochemometric modelling to correlate the properties of 317 wild-type and mutated kinases and 38 inhibitors (12,046 inhibitor-kinase combinations) to the respective combination's interaction dissociation constant (Kd). We compared six approaches for description of protein kinases and several linear and non-linear co...

• Type: Journal
• Year: 2010
• Where: BMCBI
• Authors: Maris Lapinsh, Jarl E. S. Wikberg
• Keywords: BMCBI 2010, Kinases, Mutated Kinases, Protein Kinases