
@article {8344,
	title = {An in silico approach towards the identification of novel inhibitors of the TLR-4 signaling pathway.},
	journal = {J Biomol Struct Dyn},
	volume = {34},
	year = {2016},
	month = {2016 Jun},
	pages = {1345-62},
	abstract = {<p>Precise functioning and fine-tuning of Toll-like receptor 4 (TLR4) signaling is a critical requirement for the smooth functioning of the innate immune system, since aberrant TLR4 activation causes excessive production of pro-inflammatory cytokines and interferons. This can result in life threatening conditions such as septic shock and other inflammatory disorders. The TRIF-related adaptor molecule (TRAM) adaptor protein is unique to the TLR4 signaling pathway and abrogation of TRAM-mediated TLR4 signaling is a promising strategy for developing therapeutics aimed at disrupting TRAM interactions with other components of the TLR4 signaling complex. The VIPER motif from the vaccinia virus-producing protein, A46 has been reported to disrupt TRAM-TLR4 interactions. We have exploited this information, in combination with homology modeling and docking approaches, to identify a potential binding site on TRAM lined by the BB loop and αC helix. Virtual screening of commercially available small molecules targeting the binding site enabled to short-list 12 small molecules to abrogate TRAM-mediated TLR4 signaling. Molecular dynamics and molecular mechanics calculations have been performed for the analysis of these receptor-ligand interactions.</p>
},
	issn = {1538-0254},
	doi = {10.1080/07391102.2015.1079243},
	author = {Mahita, Jarjapu and Harini, K and Rao Pichika, Mallikarjuna and Sowdhamini, Ramanathan}
}
