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MD@60: JNCASR-CECAM Conference

Vishal Kumar, a Ph.D student with Prof. U Deva Priyakumar made a poster presentation on Benchmarking different force field-water model combinations in reproducing accurate IDPs ensembles at  MD@60: JNCASR-CECAM Conference held at Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) Bangalore from 25 – 29 February. 

Here is the summary of the research work as explained by the authors Vishal Kumar, Mrudul Mete, Prathit Chatterjee, U Deva Priyakumar:

Intrinsically disordered proteins (IDPs) unlike globular proteins lack stable secondary structure and exist in the form of dynamic ensembles of conformations under physiological conditions. These conformations allow them to adapt to many roles while interacting with other proteins. It tends to interact with other IDPs, forming partially folded soluble oligomers or insoluble plaques rich in beta-sheet formation, responsible for several neurodegenerative diseases, diabetes, cancer, sickle-cell anaemia, and many more. Due to the dynamic nature of IDPs, corresponding drug discovery and development have been even more challenging. Although computational protocols have been complementarity aiding/adding to this critical problem, the choice of force fields in undertaking IDP-drug studies become challenging, in producing experimentally validated structural and dynamic parameters. Therefore, this work involves validating optimum force-field and water model combination(s) for IDP-drug interaction calculation. This will involve structural analysis by comparison of already existing experimental parameters for the IDPs. This will be followed by comparison of solvation shell dynamics for the force fields reproducing the experimental parameters more accurately, acknowledging the crucial role of water in mediating biomolecular interactions. Based on these structural and dynamic validations, IDP-drug interaction with the optimum force-field and water model pairs will be undertaken to compare their corresponding binding free energy estimation. This endeavour holds the potential to significantly enhance the accuracy in predicting interactions between IDPs and drug molecules, advancing drug discovery in the context of challenging protein structures. 

 

March 2024