Structural and Functional Annotations of Hypothetical Proteins of Candida auris for Novel Drug Target Identification: An insilico Approach

Abstract

Candida auris is an emerging fungal pathogen that causes severe invasive infections in healthcare facilities which are difficult to control and treat due to its resistance to major antifungal drugs. A large fraction of C. auris proteins are uncharacterized and hypothetical, and structural and functional characterization of these proteins can aid in the selection of novel drug targets. The present study involves a computational approach for the structural and functional characterization of hypothetical proteins from Candida auris. After the sequence
retrieval, hypothetical proteins were predicted for physiochemical properties and subcellular localization, structurally modeled using I-TASSER, quality assessed through Verify3D, ERRAT, and PROCHECK, and functionally annotated to reveal conserved domains and roles in pathogen pathways. Finally, the immunogenic assessments, non-human homologous analysis, and druggability analysis reveal three hypothetical proteins of C. auris (KND95408.2, KND95415.2, and KND95429.2) as novel drug targets. Furthermore, the stable conformations of these
selected drug targets with the minimum root mean square deviations (RMSD) and fluctuation (RMSF) were analyzed by MD simulations. Conclusively, the functional annotations of these hypothetical proteins can help in understanding the disease mechanisms at the molecular level, as well as provide new targets for drug development against Candida auris.