description): Neonatal bacterial meningitis caused by E.coli, results in a fatality rate ranging from 15% to 40%, and approximately 50% of the survivors sustain neurological sequelae. The mechanism involved in the invasion of E.coli into the central nervous system to cause meningitis is not known. It has been shown that the successful traversal of E.coli across the blood brain barrier requires the interaction of the outer membrane protein A (OmpA) on the E.coli with the host BMEC which constitutes the blood brain barrier. The objective of this proposal is to derive structure-based binding criteria for the development of effective inhibitors for the binding of the E.coli to the BMEC via OmpA. The investigators propose to use atomistic simulations to characterize the specific determinants for binding of N-acetyl glucosamine dimer(which are present on the glycoproteins in BMEC ) and its derivatives to the OmpA of E.coli. They would also determine why OmpA binds specifically to the BMEC and not to the systemic endothelial cells. The results of this proposal would provide criteria for effective binding useful in the design and testing of inhibitors for OmpA binding to BMEC.
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