Docking prediction, molecular dynamics and antibiofilm effect of linalool against Candida albicans strains from vulvovaginal secretions

Abstract

Introduction: 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.

Objective: 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.

Materials and methods: 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.

Results: 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.

Conclusions: 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.