Prospecção in silico da lactase humana e peptídeos bioinspirados: modelagem estrutural, docking molecular e modos normais.

Abstract

Lactose intolerance is one of the most prevalent metabolic conditions worldwide, caused by a deficiency of the enzyme lactase, which is responsible for lactose hydrolysis. Due to the high cost and structural complexity of this enzyme, enzymatic replacement therapy still faces limitations, prompting the search for more accessible and effective alternatives. In this study, an in silico approach was employed to model the three-dimensional structure of human lactase by homology. Based on the interaction regions with lactose, identified through molecular docking, bioinspired peptides were proposed, and their interactions with lactose were also computationally evaluated. The enzyme's structural flexibility was assessed using normal mode analysis, enabling a deeper understanding of its conformational movements. The lactase model proved to be reliable and served as the basis for peptide design, particularly highlighting the peptide derived from a sequence of amino acids within a 12 Å radius of lactose. Docking simulations for this model revealed high inhibition constants, negative binding and intermolecular energies, and the presence of strong hydrogen bonds in electropositive regions, indicating stable and thermodynamically favorable interactions. Therefore, the results suggest that both the modeled lactase structure and the designed bioinspired peptides have potential to support future research aimed at developing therapies for lactose intolerance.