Homology Modeling and Docking Studies of Bcl-2 and Bcl-xL with Small Molecule Inhibitors: Identification and Functional Studies

Title:Homology Modeling and Docking Studies of Bcl-2 and Bcl-xL with Small Molecule Inhibitors: Identification and Functional Studies

Volume: 18 Issue: 31

Author(s): Abdul Ajees Abdul Salam*, Upendra Nayek and Dhanya Sunil*

Affiliation:

• Department of Atomic and Molecular Physics, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal-576104,India

• Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal-576104,India

Keywords: Apoptosis, Bcl-2, Bcl-xL, Docking, Drug designing, Homology modeling, Indole derivatives, Protein Data Bank.

Abstract: Apoptosis is a vital physiological process, which is observed in various biological events. The anti-apoptotic and pro-apoptotic members of Bcl-2 family are the most characterized proteins which are involved in the regulation of apoptotic cell death. The anti-apoptotic proteins such as Bcl-2 and Bcl-xL prevent apoptosis, whereas pro-apoptotic members like Bax and Bak, elicit the release of caspases from death antagonists inducing apoptosis. Thus, the Bcl-2 family of proteins play a vital role in controlling programmed cell death. Over expression of anti-apoptotic Bcl-2 proteins are often directly associated with various kinds of cancer. Developing suitable inhibitors for controlling the elevated levels of these proteins got much attention in last decade. Structural biology techniques such as Nuclear Magnetic Resonance (NMR) spectroscopy, X-ray crystallography, homology modeling and molecular docking play a significant role in identifying the key inhibitors of these proteins. The authors have developed and tested successfully, several series of indole pharmacore containing inhibitors for Bcl-2 and Bcl-xL proteins based on the homology modeling, docking and suitable biochemical and apoptosis assays. This review provides a summary of potential inhibitor molecules developed for Bcl-2 and Bcl-xL proteins, as well as the the key residues of these proteins interacting with potential drug molecules. The present appraisal also focuses on the role of computational algorithms in developing potential drug molecules,with more emphasis on the role of homology modeling and docking studies in developing inhibitors for Bcl- 2, and Bcl-xL proteins in cancer therapy.

Cite this article as:

Salam Ajees Abdul Abdul *, Nayek Upendra and Sunil Dhanya *, Homology Modeling and Docking Studies of Bcl-2 and Bcl-xL with Small Molecule Inhibitors: Identification and Functional Studies, Current Topics in Medicinal Chemistry 2018; 18 (31) . https://dx.doi.org/10.2174/1568026619666190119144819