IDENTIFICATION OF ANTICANCER DRUG THROUGH STUDYING THE ACTIVATION MECHANISM OF CASPASE PROTEIN: AN IN SILICO APPROACH

Abstract

Apoptosis, a process of programmed cell death controlled by a defined apoptotic pathway, plays an important role in the development of all multicellular organisms. Any alterations in apoptotic pathways have been implicated in Cancer, one of the most deadly diseases in the world and Bangladesh as well. The pathway of Apoptosis is executed with a cascade of sequential activation of initiator and effector caspases, a family of proteases found in Apoptotic pathways to induce Apoptosis during abnormal cell growth in the cell cycle. Due to limited number of successful inhibitors in the market as well as pharmacological constraints of designed and tested peptide and peptidomimetic inhibitors against Caspase protein, In this study, In Silico approach like Virtual Screening with Molecular Docking applied to identify potential lead compounds against Pro-Caspase 7, one of the effector proteins of Apoptotic signaling proteins and 1571 drug-like molecules downloaded from the Binding database and ZINC database and identified four potential lead compounds. Noncovalent interactions like hydrogen bond, halogen bond, hydrophobic interaction, electrostatic interaction are examined among all the identified potential lead compounds and Pro-Caspase 7 after Molecular Docking study. In addition, Molecular dynamics study conducted to test the feasibility of the identified compounds in biological systems and again checked Molecular Docking energy and binding interactions for the Pro- Caspase 7 protein. Molecular dynamics study significantly increased binding energies among Pro-Caspase 7 and the first and third potential lead compounds and that are -15.8 and -14.3 kcalmol−1 respectively. Pharmacoinformatics analysis predicts that all potential lead compounds are non-carcinogenic and nonmutagenic. And, hence considering Molecular Docking study, Molecular dynamics study and Pharmacoinformatics study, the identified four potential lead compounds can induce Pro-Caspase 7 to Caspase which leads to Apoptosis and ultimately works for Cancer treatment. Although this in silico study helps the researchers and pave the way for Anti-Cancer drug development, further wet lab assessment of these potential lead compounds has to be performed.