The identification of the pathogen-associated molecular recognition patterns (PAMPs) recognition receptors for innate immunity, most notably the Toll-like receptors (TLRs), has sparked great interest in therapeutic manipulation of the innate immune system. We are devoted to the study of the molecular mechanisms involved in the TLRs functionality, and in the recognition by PAMPs, such as natural lipopolysaccharides and lipopeptides, with special focus in the design and identification of new compounds able to modulate the TLRs behaviour with possible therapeutic applications in infection, inflammation, cancer, and neurodegenerative diseases, among others.
We also pursue to deepen in antimicrobial resistance (AMR)-related molecular mechanisms, in particular: bacterial envelope and bacterial conjugation proteins. We aim at finding the unique structure-property relationships of complex bacteria envelopes in order to elucidate AMR mechanisms and, therefore, to provide molecular insights for innovative therapeutic strategies to tackle AMR. Other innovative approach is the search for inhibitors of bacterial conjugation, the most sophisticated mechanism for horizontal gene transfer. We search for conjugation inhibitors via the inactivation of some T4SS and T4CP proteins as strategy to block or, at least, reduce the resistance spread.
We combine computational methodologies at different resolution scales, from quantum to classical mechanics, such as homology modeling, protein-protein and ligand-protein docking, virtual screening, and all-atom and coarse-grained MD simulations, and works in close collaboration with international specialists in medicinal chemistry, biochemistry and cell biology.