Targeting interface HSA through anti-cancer drugs: Molecular modeling and docking

Abstract Cancer is a serious disease that takes the lives of many people all around the world each year. For treating this disease, many different chemotherapeutic drugs were discovered and examined. However, most of these drugs have serious toxic side effects. In order to reduce these side effects and increase the overall efficiency of chemotherapeutic drugs, their interaction with human deoxyribonucleic acid (DNA) and blood proteins need to be analyzed. Human serum albumin (HSA) is a protein found in human blood and due to its binding capabilities, it is responsible for transporting many drugs to affected body parts. This work aims to study binding between HSA and different anticancer drugs. For this purpose, the molecular docking approach is used. Molecular docking is a method of predicting most probable orientations between two molecules when they are bound to each other. Firstly, each subdomain of HSA and anticancer drugs were prepared and optimized in special molecular dynamic (MD) software. Then, the docking approach was used to perform docking studies and estimating interactions between drugs and HSA. A group of chemotherapy drugs (gemcitabine, fluoxymesterone, vinblastine, daunorubicin and ergosterol peroxide) were selected for docking simulation. Results of the docking studies provided scores for possible conformations between each subdomain of HSA and each drug. Best scores represented the most possible conformations of drug-protein interactions with the lowest binding energy. The pose prediction has been made by identifying the correct binding modes. Affinity ranking for different drugs and subdomains were performed.