VIRTUAL SCREENING OF HETEROBASED LIGAND LIBRARY FOR PROTEIN KINASE INHIBITOR FOR ANTICANCER ACTIVITY

Incorporating receptor flexibility is considered crucial for improvement of docking based virtual screening with an abundance of crystallographic structure are freely available, docking with multiple crystal structure is believed to be a practical approach to cope with protein flexibility.2SRC structures were first compared in a single structure docking by predicting the binding mode and recovering known ligands. Combination of different protein structures were compared by recovery of known ligands and an optional ensemble of 2SRC structure were selected. The chosen structure was used in virtual screening of over 2700 diverse compounds for 2SRC inhibitors. Six novel drugs ranked at the top of the hits list were tested experimentally proved. Further study indicated that achieving a better enrichment and identifying more diverse compounds was more likely using multiple structures than using only a single structure ever when protein structure were randomly selected. Taking into account conformational energy difference did not help to improve enrichment in the top ranked list.