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Talk- Rupesh Agarwal

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  • cmb seminar
When Jan 22, 2018
from 11:00 AM to 12:30 PM
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Stopping the “glue” protein from sticking

 Infective endocarditis is a life-threatening cardiovascular infection associated with significant morbidity and mortality. Although the pathogenesis of this disease is not well understood, adherence of causative bacteria to the host platelets is the first major step for biofilm formation and disease development. Endocarditis-associated Viridans streptococci often contain an adhesin protein that can attach to the platelets via sialoglycans on the human GP1b receptor. Sequence analysis has revealed that sialoglycan-binding adhesins can be divided into three branches and so far, we have six crystal structures (two structures from branch 1 and four structures from branch 2). Currently, there are no known inhibitors that target the sialoglycan-binding sites in the adhesin proteins. In our current study, we aim to computationally predict compounds that can disrupt the formation of the adhesin protein:sialoglycan complex, and thus prevent the initiation and progression of infection. We have performed high throughput in-silico screening of the Vanderbilt small molecule dataset (100,000 compounds) to an ensemble of all six adhesin structures using VinaMPI. The ensembles were constructed from molecular dynamics (MD) simulations and the crystal structures. The compounds have been ranked based on the AutodockVina scoring function. Additionally, we also aim to understand the importance of global and local dynamics of these multi-domain adhesin proteins on the binding site.


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