Docking prediction, molecular dynamics and antibiofilm effect of linalool against Candida albicans strains from vulvovaginal secretions.
Source: PubMed, NCBI / U.S. National Library of Medicine
Vulvovaginal candidiasis is a prevalent fungal infection, predominantly caused by Candida albicans. Biofilm formation plays a central role in disease persistence and therapeutic failure by enhancing fungal tolerance to conventional antifungal agents. To evaluate the antibiofilm activity of linalool against C. albicans strains isolated from vulvovaginal secretions and to investigate its potential molecular interactions with 1,3-β-glucan synthase, a key enzyme involved in fungal cell wall biosynthesis. The antibiofilm effect of linalool was assessed in vitro using the crystal violet assay against a clinical isolate (C. albicans LM 129) and a reference strain (C. albicans ATCC 76485). Nystatin was included as a comparator antifungal. In parallel, molecular docking analyses were performed using AutoDock 4.2, followed by molecular dynamics simulations conducted in GROMACS 2022.3 to evaluate the stability of the linalool-enzyme complex. Linalool significantly reduced biofilm formation in both C. albicans strains, with an average inhibition of 74.65%, whereas nystatin exhibited limited antibiofilm activity. Docking studies revealed that linalool interacts with the active site of 1,3-β-glucan synthase, presenting a binding free energy (ΔG) of -6.0 kcal/mol, comparable to the control ligand castanospermine (-7.0 kcal/mol). Molecular dynamics simulations demonstrated structural stability of the linalool-enzyme complex over a 30 ns trajectory, supporting the persistenc
Abstract
Vulvovaginal candidiasis is a prevalent fungal infection, predominantly caused by Candida albicans. Biofilm formation plays a central role in disease persistence and therapeutic failure by enhancing fungal tolerance to conventional antifungal agents. To evaluate the antibiofilm activity of linalool against C. albicans strains isolated from vulvovaginal secretions and to investigate its potential molecular interactions with 1,3-β-glucan synthase, a key enzyme involved in fungal cell wall biosynthesis. The antibiofilm effect of linalool was assessed in vitro using the crystal violet assay against a clinical isolate (C. albicans LM 129) and a reference strain (C. albicans ATCC 76485). Nystatin was included as a comparator antifungal. In parallel, molecular docking analyses were performed using AutoDock 4.2, followed by molecular dynamics simulations conducted in GROMACS 2022.3 to evaluate the stability of the linalool-enzyme complex. Linalool significantly reduced biofilm formation in both C. albicans strains, with an average inhibition of 74.65%, whereas nystatin exhibited limited antibiofilm activity. Docking studies revealed that linalool interacts with the active site of 1,3-β-glucan synthase, presenting a binding free energy (ΔG) of -6.0 kcal/mol, comparable to the control ligand castanospermine (-7.0 kcal/mol). Molecular dynamics simulations demonstrated structural stability of the linalool-enzyme complex over a 30 ns trajectory, supporting the persistence of these interactions under dynamic conditions. Linalool exhibits relevant antibiofilm activity against C. albicans and shows stable interactions with 1,3-β-glucan synthase, suggesting a plausible inhibitory mechanism. These findings support the potential of linalool as a natural scaffold for the development of alternative therapeutic strategies for vulvovaginal candidiasis.