High Throughput Structural Biology and In Silico Screening Identify Novel Antibacterial Drug Candidate
The Special Projects Group at NYSBC has built a pipeline to clone, express, purify, and determine the structures of proteins from Coxiella burnetii, a highly infectious pathogen that can cause disease in humans and other mammals. In under ten months, this group analyzed all 1847 protein-coding genes of C. burnetii, cloned 500 of these genes, purified 200 proteins to crystallization grade, and solved 48 X-ray crystal structures.
Structural information can guide the identification of more specific therapeutic agents. Left: a compound was identified by in silico screening predicted to bind the bacterial (gray) but not human (blue, steric clash in red) DHFR, and an in vitro assay confirmed this specificity.
Research article: Franklin et al. 2015, Proteins. PMID: 26033498