Bioactive structures for inhibitors of Candida auris polymerase enzyme by artificial intelligence
Francisco das Chagas Lima Pinto, Sadrack Queque Cabongo, Pedro Ferreira Barbosa Joao, Manuela Polidoro Lima, Maria Mabelle Pereira Costa Paiva, Junilson Martinho Canjanja Madureira, Bernardino Joaquim Caluaco, Regilany Paulo Colares, Moisés Maia Neto, Hélcio Silva dos Santos, Emmanuel Silva Marinho, Aluísio Marques da Fonseca · Future Medicinal Chemistry · 2025
Aims Present new bioactive compounds, created by De novo Drug Design and artificial intelligence (AI), as possible inhibitors of C. auris polymerase.Materials & Methods MolAICal’s AI module was configured to identify FDA-approved molecular fragments with therapeutic effectiveness against C. auris polymerase, where the model with optimized synthetic accessibility and structural complexity was subjected to docking and molecular dynamics simulations and pharmacokinetic prediction.Results Among 1,722 new forms, the Hit-960 compound stood out for its high bioaffinity and stability, with a binding energy of −9.12 kcal/mol and 75% synthetic accessibility.Conclusions Clinical studies are recommended to test its efficacy, contributing to the development of new treatments for C. auris infections.