Homology Modeling and Molecular Dynamic Study of Candida Albicans Heat Shock Protein 21, a Potential Target Protein for Antifungal Drug Development

Background: Species of Candida are ranked as the third most frequently isolated pathogens from blood. Although, Candida albicans (C. albicans) are one of the main etiologic agent for candidiasis, the small heat shock protein 21 (sHsp21) in C. albicans showed its pivotal role for environmental stress adaptation and fungal virulence. In C. albicans Hsp21 is a necessary factor for thermal and oxidative stress tolerance. Results: In the present work a homology model of Hsp21 from C. albicans was developed and evaluated using validated methods. Ramachandran plot for the model demonstrated that 98.02 percent of residues are in most favorable region, indicating that the model is reliable. The computed energy value, instability index and root mean square deviation (RMSD) fluctuation of back bone alpha carbon of the model, confirming the stability of the model. Molecular dynamics simulations in explicit solvent environments were carried out for the entire protein by using Molecular Operating Environment (MOE) with AMBER99 force field with the aim to characterize the dynamics of the protein. The results showed an open motion of the protein in solvent. Conclusions: Until the determination of three-dimensional structure of Hsp21 experimentally, the predicted model will serve as a supportive reference for exploring the interactions between Hsp21 and its antagonists. This research might help to understand the mechanism of action of Hsp21 protein and might facilitate the design of new and potent chemo-types to combat infection caused by Candida albicans.