Browsing by Author "Mabonga, Lloyd"

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    Analysis of the biophysical and in silico exploration of the interaction between small ribonucleoprotein G and the RING finger domain of retinoblastoma binding protein 6 for the identification of protein anti-cancer compounds
    (University of Zululand, 2021) Mabonga, Lloyd
    Cancer is the second leading cause of death globally after cardiovascular diseases, killing more people than HIV/AIDS, tuberculosis and malaria combined, which makes it a major public health concern. Increasing cancer morbidity and mortality rates has partly been due to the lack of specificity and side effects associated with most cancer drugs; hence over the years tremendous efforts have been linked to finding solutions to address these challenges. Novel techniques to design and develop cancer treatment methods using protein-protein interactions (PPIs) have become promising targets for therapeutic discovery. Suggestive evidence has proposed putative interactions between Small nuclear ribonucleoprotein polypeptide G (SNRPG) (also referred to as SmG in this study) and retinoblastoma binding protein 6 (RBBP6), which have been identified as potential diagnostic markers for cancer treatment. The broad focus of this study was to investigate the putative interactions between these two proteins. In-silico analysis and characterisation of the proteins using Autodock Vina revealed the binding and interaction patterns of SNRPG with the RBBP6 RING Finger domain with a docking score of 3.40kcal/mol. Using I-TASSER, a potential inhibitor known as (2R)-2-[(2-methyl-5-phenylpyrazol-3-yl) carbonyl amino]-3-napthalen-2-yl-propanoic acid) (4FI) was identified and MM/GBSA binding free energy analysis revealed a spontaneous reaction of SNRPG~RING Finger domain in complex with the inhibitor, due to a binding energy of -27.96kcal/mol. Some of the amino acid residues involved in the binding include Val222, Pro101 and Met194. Biophysical studies using MicroScale Thermophoresis (MST) confirmed the putative SNRPG~RING Finger domain interaction, and determined that the binding affinity was a Kdvalue of 3.1596 nM under aqueous buffer conditions. The overall results from this study suggest the potential druggability of the SNRPG~RING Finger domain PPI. These findings will enhance our understanding in selective identification of small molecule inhibitors or peptides, which could be developed as novel therapeutic candidates in the diagnosis and treatment of cancer.