Computational study to evaluate the potency of phytochemicals in Boerhavia diffusa and the impact of point mutation on cyclin-dependent kinase 2-associated protein 1

A protein's function is closely related to its structural properties. Mutations can affect the functionality of a protein. Different cancer tissues have found disordered expression of the cyclin-dependent kinase 2-associated Protein 1 (CDK2AP1) gene. A protein molecule's conformational flexibility affects its interaction with phytochemicals and their biological partners at various levels. Boerhavia diffusa has been investigated most extensively for its medicinal activities like anticancer properties. It contains many bioactive compounds like Boeravinone A, Boeravinone B, Boeravinone C, Boeravinone D, Boeravinone E, Boeravinone F, Boeravinone G, Boeravinone H, Boeravinone I and Boeravinone J. We have studied to analyse the binding efficacy properties as well as essential dynamic behaviour, free energy landscape of both the native and mutant protein CDK2AP1 with bioactive compounds from Boerhavia diffusa plant extracts through computational approaches by homology modelling, docking and molecular dynamics simulation. From the molecular docking study, we found that. Boeravinone J have best binding affinity (–7.9 kcal/mol) towards the native protein of CDKAP1 compared to others phytochemicals. However, we found the binding energy for H23R and C105R (mutation point) −7.8 and −7.6 kcal/mol, respectively. A single minima energy point (from 100 ns molecular dynamics simulation study) was found in the H23R mutant with Boeravinone J complex suggested that minimum structural changes with less conformational mobility compared C105A mutant model. Communicated by Ramaswamy H. Sarma