There has been an exponential increase in the design of synthetic antimicrobial peptides (AMPs) for its use as novel antibiotics. Synthetic AMPs are substantially enriched in residues with physicochemical properties known to be critical for antimicrobial activity; such as positive charge, hydrophobicity, and higher alpha helical propensity. The current prediction algorithms for AMPs have been developed using AMP sequences from natural sources and hence do not perform well for synthetic peptides. In this version of CAMP database, along with updating sequence information of AMPs, we have created separate prediction algorithms for natural and synthetic AMPs. CAMPR4 holds 24243 AMP sequences, 933 structures, 2143 patents and 263 AMP family signatures. In addition to the data on sequences, source organisms, target organisms, minimum inhibitory and hemolytic concentrations, CAMPR4 provides information on N and C terminal modifications and presence of unusual amino acids, as applicable. The database is integrated with tools for AMP prediction and rational design (natural and synthetic AMPs), sequence (BLAST and clustal omega), structure (VAST) and family analysis (PRATT, ScanProsite, CAMPSign). The data along with the algorithms of CAMPR4 will aid to enhance AMP research. CAMPR4 is accessible at http://camp.bicnirrh.res.in/.
For widening the therapeutic options for Candida management, the druggability of Candida proteome was systematically investigated using an innovative pipeline of high-throughput data mining algorithms, followed by in vitro validation of the observations. Through this exercise, HIV-1 protease was found to share structural similarity with secreted aspartyl protease-3 (SAP3), a virulence protein of Candida.Using the molecular fingerprint of HIV-1 protease inhibitor GRL-09510, we performed virtual screening of peptidomimetic library followed by high-precision docking and MD simulations for discovery of SAP inhibitors. Wet-lab validation of the four shortlisted peptidomimetics revealed that two molecules, when used in combination with fluconazole, could significantly reduce the dosage of fluconazole required for 50% inhibition of Candida albicans. The SAP inhibitory activity of these peptidomimetics was confirmed through SAP assays and found to be on par with pepstatin A, a known peptidomimetic inhibitor of aspartyl proteases.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.