Molecular dynamics simulations of aqueous systems of inhibitor candidates for adenosine-5’-phosphosufate reductase

Abstract

Molecular dynamics (MD) simulations were used to evaluate some chelating agents as potential candidates to inhibitors for dissimilatory adenosine-5’-phosphosulfate reductase (APSrAB). Molecular docking methods were used to evaluate the best binding modes of these molecules to the enzyme at two binding sites: of the substrate (enzyme active site) by mean the redocking protocol of substrate; and of one of the [Fe₄S₄]²⁺ groups by mean of the clusterization protocol. The best docking poses were selected by criteria such as low energy and RMSD (redocking) and the cluster with the higher number of similar poses (clusterization), which were submitted to MD simulations. RMSD, RDF, and hydrogen bonds results revelated that all ligands left the cube site, while in the active site, some ligands remained in their docking region, pointing to the enzyme active site as the best target for the selected ligands. The binding energy results of ligands hydroxamic acid (HXA) and catechol (CAT) showed that they bonded favorably to the enzyme and key residues of the active site contributed significantly to the protein-ligand bind, indicating HAX and CAT may compete with the substrate for interactions with these residues and displaying potential as candidates for experimental studies about APSrAB inhibitors.

Communicated by Ramaswamy H. Sarma

Keywords:

• Dissimilatory adenosine-5’-phosphosulfate reductase
• sulfate-reducing bacteria
• molecular dynamics simulations
• molecular docking

Acknowledgements

This study was financed by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil) (Financial code 001; PhD Scholarship for TU da Silva; MSc Scholarship for KC Pougy). The authors also thank the FAPERJ (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro) (scolarship E-26/010.210.513/2019) and CNPq (Conselho Nacional de Desenvolvimento Científico) (grant 304402/2017). This research was developed with the help of the CENAPAD-SP (Centro Nacional de Processamento de Alto Desempenho em São Paulo), UNICAMP/FINEP-MCT (Universidade Federal de Campinas/Financiadora de Estudos e Projetos do Ministério da Ciência, Tecnologia e Inovação, Brasil) Project (proj 835).