Chemical Descriptors, ADMET, Molecular Docking and Molecular Dynamics Simulation of Mannopyranoside Derivatives against Smallpox Virus Proteins

Employing computer-aided drug design techniques, the physicochemical, biological, and pharmacokinetic properties of several derivatives of methyl α-D-mannopyranoside were explored. Geometrical optimization was conducted using density functional theory (DFT) with a ۳-۲۱G basis set, yielding crucial insights into the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). From these data, softness, electron affinity, ionization potential, electronegativity, hardness, electrophilicity, and chemical potential were derived. Notably, compound ۱ (mannopyranoside) exhibited the widest energy gap (۰.۲۷۴۳۹ eV), while compound ۴ (lauryl derivatives) displayed the narrowest energy gap (۰.۰۱۹۲۴ eV). Furthermore, comprehensive studies encompassing geometrical, thermodynamic, molecular orbital, and electrostatic potential analyses were conducted to elucidate the physical and chemical behavior of the compounds. Molecular docking against the Smallpox virus (PDB ۳IGC) proteins enabled the investigation of binding affinity, mode, and interactions with the receptor. ADMET prediction was employed to compare the absorption, distribution, metabolism, and toxicity of the compounds, revealing that compound ۶ (a palmitoyl derivative) has the highest free energy and internal energy. A ۱۰۰ ns molecular dynamics (MD) simulation was used to observe the complex structure formed by the ۳IGC protein under in silico physiological conditions to determine its stability over time. It showed a stable conformation and binding pattern in a stimulating mannopyranoside derivative environment. Overall, this study provides valuable insights into the biochemical impact of these compounds on the environment and the human body, offering significant implications for future research endeavors. These findings suggest promising prospects for the development of effective antiviral agents targeting smallpox.

Keywords:

Glucopyranoside , DFT , Molecular docking , MD simulation , ADMET , Smallpox