Cargando…

Prediction of kinase-inhibitor binding affinity using energetic parameters

The combination of physicochemical properties and energetic parameters derived from protein-ligand complexes play a vital role in determining the biological activity of a molecule. In the present work, protein-ligand interaction energy along with logP values was used to predict the experimental log...

Descripción completa

Detalles Bibliográficos
Autores principales: Usha, Singaravelu, Selvaraj, Samuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Biomedical Informatics 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5267961/
https://www.ncbi.nlm.nih.gov/pubmed/28149052
http://dx.doi.org/10.6026/97320630012172
Descripción
Sumario:The combination of physicochemical properties and energetic parameters derived from protein-ligand complexes play a vital role in determining the biological activity of a molecule. In the present work, protein-ligand interaction energy along with logP values was used to predict the experimental log (IC50) values of 25 different kinase-inhibitors using multiple regressions which gave a correlation coefficient of 0.93. The regression equation obtained was tested on 93 kinase-inhibitor complexes and an average deviation of 0.92 from the experimental log IC50 values was shown. The same set of descriptors was used to predict binding affinities for a test set of five individual kinase families, with correlation values > 0.9. We show that the protein-ligand interaction energies and partition coefficient values form the major deterministic factors for binding affinity of the ligand for its receptor.