Computational evaluation of new homologous down regulators of translationally controlled tumor protein (TCTP) targeted for tumor reversion

Abstract

The Translationally Controlled Tumor Protein (TCTP) has been investigated for tumor reversion and is a target of cancer therapy. Down regulators which suppress the expression of TCTP can trigger the process of tumor reversion leading to the transformation of tumor cells into revertant cells. The present investigation is a novel protein-protein docking approach to target TCTP by a set of proteins similar to the protein: sorting nexin 6 (SNX6) which is an established down regulator of TCTP. The established down regulator along with its set of most similar proteins were modeled using the PYTHON based software - MODELLER v9.9, followed by structure validation using the Procheck Package. Further TCTP was docked with its established and prospective down regulators using the flexible docking protocol suite HADDOCK. The results were evaluated and ranked according to the RMSD values of the complex and the HADDOCK score, which is a weighted sum of van der Waal's energy, electrostatic energy, restraints violation energy and desolvation energy. Results concluded the protein sorting nexin 6 of Mus musculus to be a better down regulator of TCTP, as compared to the suggested down regulator (Homo sapiens snx6).

Design of novel JAK3 Inhibitors towards Rheumatoid Arthritis using molecular docking analysis

“…An 'unnamed complex' structure file was created in this folder. This structure file was opened with the help of Molegro and all constraints, cavities, and ligands in the structure were removed to obtain only the protein structure [62-63]. The best pose of the drug was tallied from the result generated and was then imported.…”

Structure based virtual screening of ligands to identify cysteinyl leukotriene receptor 1 antagonist

“…Since the three dimensional structure of human cysteinyl leukotriene receptor 1 was not available in Protein Data Bank, the structure was generated in silico [ 22 ]. The sequence of receptor was retrieved from NCBI (Accession Number: NP_006630.1) which was then blasted against Protein Data Bank database.…”

Molecular docking analysis of RN18 and VEC5 in A3G-Vif inhibition

“…The build_profile.py was used for the local dynamic algorithm to identify homologous sequences against target Vif Target sequence. The final model obtained from modeler further been used for structure validation using Procheck [ 23 , 24 ].…”