Interaction of Proteins with small Molecules and Peptides

Pal, Uttam (2016) Interaction of Proteins with small Molecules and Peptides. PhD thesis, J U .


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    Maiti, Nakul Chandra


    Understanding the molecular interaction of proteins with small molecules and peptides is essential in drug discovery. This thesis explores the importance of protein small molecule interactions in biology and its implications in rational drug development. Using combined theoretical and experimental chemistry, author tried to device new approaches or build upon the existing tools to study the interactions of proteins with small molecules and peptides. New algorithm has been developed based on the existing molecular docking methods to improve the specificity in docking prediction and reduce the false positive results (hits) in virtual high throughput screening. In recent years allosteric drugs have gained much attention because of the specificity it can achieve due to the evolutionarily diverse binding sites on the target proteins. The author developed a pattern based approach using molecular docking tools to detect the allosteric binding sites on structured protein targets and analyzed the druggability of these allosteric binding sites. Detections of binding sites in the intrinsically disordered proteins was also explored using the sequence based analysis tools. Statistical distribution of binding sites in a library of disordered proteins was characterized. A fluorescent probe molecule has been developed to study the microenvironment of protein binding sites, which showed increased quantum yield, anisotropy and higher energy emission upon binding to a hydrophobic site of the target protein. Author studied even deeper into the finer details of molecular interactions such as the hydrogen bonding and its strength on model system (alcohol amine complexes) using isotope labeling, solution state nuclear magnetic resonance spectroscopy and quantum mechanics with implications in protein small molecule interactions.

    Item Type: Thesis (PhD)
    Subjects: Structural Biology & Bioinformatics
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Ms Sutapa Ganguly
    Date Deposited: 09 Sep 2016 15:55
    Last Modified: 26 Oct 2016 11:46

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