Comprehensive Molecular Modeling Analysis of Betulin, a Triterpene Isolated from <i>Miconia burchellii</i> (Melastomataceae) Native to the Brazilian Cerrado

Abstract Betulin, a naturally occurring pentacyclic triterpenoid extracted from Brazilian Cerrado vegetation, was isolated and characterized using single‐crystal X‐ray diffraction. The solid‐state structural analysis revealed H⋯H contacts and O⋯H interactions that stabilize the supramolecular architecture, which includes two independent conforms. Additionally, density functional theory calculations at the M06‐2X/6‐311++G(d,p) level were carried out, providing optimized geometry, electronic distribution insights, and frontier molecular orbitals. The computed HOMO‐LUMO energy gap (9.38 eV) suggested moderate chemical reactivity and molecular stability. Furthermore, molecular electrostatic potential mapping highlighted electron‐rich regions pertinent to biological interaction. Molecular docking simulations were performed to predict the binding affinity of betulin molecule with cytochrome P450 17A1 – a prostate cancer‐associated protein target. The docking outcomes revealed stable interactions and binding sites consistent with reported pharmacological activities. This comprehensive study, combining solid state analysis, advanced molecular modeling, and pharmacophoric analysis, deepens the understanding of structural behavior of betulin and its potential as a bioactive compound.