Docking and simulation Studies on CDK4 for targeting Cell cycle Arrest in Cancer using Flavanone and its Congener

Abstract

Abstract Flavanone compounds are naturally occurring phytochemicals present in most of citrus fruits reported to be a potential anticancer moiety as it majorly participates in inhibition of cell cycle, apoptosis, and Angiogenesis. Because of poor bioavailability Natural Flavanones were not used as therapeutic targets so flavanone congeners was prepared by Modifying at B-functional group using compound libraries such as Drugbank, PubChem, Sellkchem Database .Cyclin dependent Kinase is primarily activating cell cycle and potentiating M phase, in order to control cell cycle in cancer Cyclin dependent pathway was targeted and potential CDK4 Receptor protein was retrieved from Protein Data Bank (PDBID:2W9Z).Binding site was determined using FlexX docking. Flavanone and its congeners were docked against 2W9Z receptor Protein with docking software FlexX. For validation of docking results Molecular Dynamics simulations of the best fitting molecule were carried out using Desmond Package. Noncovalent interactions like hydrogen bond, electrostatic interaction, and Vander walls potentials for stable conformations were calculated. Thus upon docking and molecular dynamics studies we discovered the potential flavanone derivatives such as Flavanone 20, flavanone 23,and flavanone 29 will become a potential drug target in controlling cell cycle arrest and may become a futuristic candidate in targeting cancer