Shaikh Uzma Jamal1, Manoj Kumar2, Md. Imtaiyaz Hassan3, Punit Kaur2
1Department of Computer Science, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
2Department of Biophysics, All India Institute of Medical Sciences, New Delhi-110029, India.
3Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
Kallikrein-related peptidases (KLKs) have been found to be over-expressed in several types of cancer and hence it makes them clinically relevant biomarkers for diagnosis, prognosis and monitoring. The KLKs are trypsin-like serine proteases. The human KLKs can be subdivided into in several tissue-specific groups based on location, physiological substrates and functions. The human KLK6, a tissue kallikrein, is highly expressed in ovarian cancer as well as in neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, inflammatory disease and demyelination. It is involved in the tumor progression and cancer metastasis and this makes it a potential therapeutic target in anti cancer therapies. Hence, it can be exploited as an excellent drug target for cancer chemotherapy as the down regulation of excessive KLK activity by small molecule inhibitors may yield attractive therapeutics. The available small molecule inhibitors of KLKs lack the specificity and hence cause cytotoxicity. Thus, the synthesis of biotolerable drugs or the engineering of biomolecules from natural sources is required. In silico drug discovery is emerging rapidly because of its time and cost cutting in the field of drug discovery. We have employed computational techniques to design a potent inhibitor of human KLK6 using virtual screening approach. Molecular dynamics simulation was performed on human KLK6 complexed to the best inhibitor identified and its binding stability was verified in the presence of water solvents. Thus, it could provide a potential inhibitor for the development of cancer chemotherapeutics. Read more…