Bio-molecular optimized interactions and conformational switches in human ERβ and SRC-1 protein: An in silico approach to suppress tumor in breast cancer malignancies: Computational insight for suppression of tumorigenesis in breast malignancies

摘要

A vital female hormone; estrogen activates the β-subunit of estrogen receptor protein (ERβ), which further aids in the suppression of the breast tumor cells with the aid of human SRC-1 (steroid receptor coactivator-1) protein. Though wet laboratory documentation has been documented on this regard but the molecular level studies via optimization operations remains yet unexplored. So, for the purpose, experimentally validated 3D functional structures of the two essential human proteins; ERβ and SRC-1 were extracted, demonstrated and analyzed. Protein-protein docking further led to the complex formation, which was further subjected to optimization and molecular dynamics simulation techniques. Residual contribution from the pre optimized and post optimized simulated protein-protein complex was compared and examined individually, with an additional focus on the binding patterns. The increase in the predominant ionic interactions and side chain-side chain interactions displays the optimized and simulated complex to be greatly interactive one. Mainly, polar negatively charged; Asp87 from ERβ and His1, His5 and Lys2 from SRC-1 played a pivotal role in the protein interaction mechanism after optimization followed by simulation. Statistically significant evaluations from free energy of folding, net area available for solvent accessibility, electrostatic surface potential as well as conformational transition from coils to helices in either of the two proteins additionally affirms the structures to gain stability and strength after optimization and simulation. Therefore, this present study provides a scope to view the residual interactive mode and the most stable interactive protein structures responsible for hindering the tumor proliferation in human breast cancers. For future, it further instigates the biomedical and pharmaceutical field for breast cancer malignancies.