Core 4: Biology and Chemistry Summary CRNA investigators in this Core component have a wide range of expertise in virology, cell and molecular biology, RNA biology, and chemistry. Each of the biologically focused projects requires the application of techniques and expertise in these areas. To facilitate the identification of new targets for structural and biophysical analysis, the validation and biological interpretation of structural and biophysical data, and the identification of lead small molecule chemical probes, the Biology and Chemistry Core will undertake a number of activities including: (1) the discovery of new features of HIV-1 RNAs and HIV-1 RNA-protein complexes for structure function studies using next-generation sequencing-based approaches, (2) HyPR-MS, siRNA and sCAS9/SAM (CRISPR) screening to identify and validate new protein targets for structure-function studies, (3) the provision of virology and general molecular biology support to biologically and structurally focused projects and aims, and (4) in silico, in vitro and in cell RNA-targeted screening and chemical synthesis along with cheminformatics / machine learning techniques to enable the discovery of RNA-targeted inhibitors of the biological processes studied in the CRNA.