Insilico modeling and analysis of small molecules binding to the PHLPP1 protein by molecular dynamics simulation

The PHLPP (Pleckstrin homology domain leucine-rich repeat protein phosphatases) is a newly discovered group of genes which includes PHLPP1 and PHLPP2 and plays an integral part in several cellular processes like apoptosis, cell signaling cell survival, and cell proliferation etc. Both the activation and deactivation of these genes can have vital role in several ailments like heart diseases, circadian rhythm and most importantly the cancer, hence encouraging the growth of novel therapeutic elements. To give new directions into the development of PHLPP1-targeting drugs, the interaction mechanism between PHLPP1 and five important ligands 4IP, B39, 635, ATP and GTA were investigated through docking and Molecular Dynamics Simulation. It is also noteworthy to be mentioned here that there is no previous crystal structure of PHLPP1 available. The in-silico results can provide potential base for advancements in development of new therapeutic elements targeting different diseases, mainly cancer. In this study, we employed homology modeling technique to develop a high-quality structure model of PHLPP1. The PHLPP1 model was then used in docking interaction analysis and Molecular Dynamics Simulation, to study binding pockets and interactions of PHLPP1 ligands and finding actively contributing residues in binding pocket. In final step, Free Energy Estimation was performed to observe ligand binding's quantitative characteristics.