Assessing the Specificity of Paclitaxel towards the Marker Proteins of Breast Cancer Using In silico Molecular Docking Study

Abstract

Breast cancer is highly prevalent next to lung cancer. Breast cancer occurs as a result of mutation in the genes like proto-oncogenes as well as tumor suppressor genes in a single clone of cells in the ductal and glandular regions of the breast. The drugs used to prevent breast cancer are Raloxifene hydrochloride and Tamoxifen citrate. The drugs used to treat breast cancer are Abemaciclib, Paclitaxel, Everolimus, Imatinib, Alpelisib, Anastrozole. Although several drug molecules had been developed, their specificity towards the potential breast cancer specific marker proteins such as activated threonine kinase 2/Protein kinase B (AKT2), cell division protein kinase 6 (CDK6), estrogen receptor (ER), human epidermal growth factor receptor type 2 (HER2), and poly ADP ribose polymerase1 (PARP1) need to be studied in silico. The present study was undertaken 1) to assess the specificity of paclitaxel towards the breast cancer specific marker proteins using molecular docking analysis and 2) to identify various physico-chemical properties of drug molecules including absorption, distribution, metabolism and excretion (ADME). The interaction between paclitaxel and the target proteins of breast cancer was analyzed using the Schrodinger Maestro Ver.2018.4. The results of the present study reveal that paclitaxel shows good binding interactions with the target proteins in the following order, ER > PARP1 > AKT2 >CDK6 > HER2. Among the five proteins, ER and PARP1 showed good binding interactions as compared to AKT2, CDK6 and HER2 proteins. The ADME properties of paclitaxel were predicted using QikProp module of Schrodinger Maestro version 2018.4. The present study warrant further studies which helps in the development of potent anticancer drug to treat breast cancer.