3D-QSAR, molecular docking, molecular dynamic simulation, and ADMET study of bioactive compounds against candida albicans

Candida albicans has developed significant levels of resistance to traditional antifungals. posing a danger to world health. In this research, the potential inhibitory of a class of twenty-five triazole molecules revealed an activity against candida albicans was addressed by using the three dimensional quantitative structure-activity relationship approach. The reliable models developed by CoMFA and CoMSIA/SEA exhibited high values of Q(2) (0.620 and 0.733) respectively, and notable values of R-2 (0.840 and 0.890) respectively. CoMFA and CoMSIA/SEA contour maps bring a set of information that may be invested to identify the key sites that have an important influence on the candida albicans activity. These findings lead us to design four new triazole compounds with good predicted activity. The new triazole molecules were undergone to in-depth study by assessing their oral bioavailability and toxicity using in silico ADMET prediction. The new molecules T1, T2 and T3 exhibited good properties in tenns of numerous pharmacokinetics parameters as absorption, BBB penetration and toxicity. In addition, molecular docking was conducted to identify the types and mode of interactions between triazole ligands and the receptors. The reached findings appeared the high stability of the new triazole scaffolds at the active site of the receptor (PDB code: 2Y7L). The molecule T1 which is exhibited good stability in the active pocket of the receptor was further subjected to a molecular dynamics (MD) simulation using 20 ns in order to scrutinize the protein's comparative conformational dynamics following ligand binding. MD simulation for 20 ns reveals promising results for the molecule T1.