ANALYSIS OF THE INTERACTION BETWEEN HYDROGEN SULFIDE AND RECEPTORS OF HYPOXIA-INDUCABLE FACTORS THROUGH MOLECULAR DOCKING: AN IN-SILICO EXPERIMENT

• DOI: https://doi.org/10.22533/at.ed.1594472429057

• Palavras-chave: Molecular Docking. Computational Simulation. Oxidative stress

• Keywords: Molecular Docking. Computational Simulation. Oxidative stress

• Abstract:

  Hydrogen sulfide (H2S) is a small gaseous molecule that, despite being known as a toxic and smelly gas derived from decomposition processes, has physiological properties similar to other gases in the human body, such as nitric oxide, acting as a gasotransmitter. Animal studies have demonstrated that H2S has an anti-inflammatory role during systemic infections and periods of physiological stress. Hypoxia-inducible factors (HIFs) are critical regulators of human homeostasis, managing oxygen supply and demand to cells. This system is frequently exploited by cancer cells, as its hyperactivation promotes gene transcription, cell division and angiogenesis, facilitating nutrition and cancer dissemination. Molecular docking is a technique that positions two individual structures and simulates their interactions, classifying different possibilities of connection. This experimental tool directs in vitro and in vivo studies, minimizing the risk of failure. The present work consists of an in silico experimental study that investigated the interaction between H2S and HIF receptors through molecular docking simulations. The PDB codes 1h2k, 1h2l, 1h2m, 30d4, 2ilm, 5tbm, 3f1n, 6x28, 4wn5 and 7v7w were used to simulate HIFs receivers. Hydrogens were added separately to receptors and ligands, and Gasteiger charges were calculated using ADT software, including nonpolar hydrogens. 

  
  The dimensions of the grid box were set to 30 Å for each axis, positioned at the coordinates of the atoms in the active site region and at the interface. In the experiments, a minimum binding energy of 0.9 kcal/mol was observed between H2S and the tested HIF receptors, indicating a reduced interaction of the gas with the receptor, in contrast to the existing literature. Possible explanations include limitations of computational models and the simplification of molecular docking mechanisms, which may not capture all interactions between H2S and HIFs. The choice of predefined coordinates in a specific active site of the proteins and variations in the three-dimensional structure of the receptors and H2S can also influence the binding affinity results. Therefore, there is a need for more studies to understand the metabolic pathway of HIF receptors and the influence of H2S in inhibiting this pathway and combating oxidative stress. Despite the low affinity observed between H2S and HIF in the molecular docking study, these results are significant and offer valuable insights, contributing to knowledge about the interaction between H2S and HIF. They indicate that, under the conditions tested, there is no strong connection between the two entities, suggesting the need for additional investigations to explore other possible interactions between H2S and HIF in different experimental conditions or considering other factors, such as post-translational modifications of the proteins.