Molecular Dynamics Discovers Ligand Binding Regions on Molybdate Transport Protein, Moda

In the pharmaceutical industry, many protein crystal structures are labeled as “undruggable” due their lack of suitable crevices for binding of ligands, when viewed under static frames, through static docking. Our hypothesis is that the majority of proteins do have ligand binding sites when assessed dynamically. The focal point of this research was to utilize computational molecular dynamics in order to study the binding behavioral patterns of the Molybdate Binding Protein, ModA. This protein was tested on all 20 amino acids and bound to additional common functional groups, which revealed unknown binding sites on protein. The binding energies of the compounds on the protein increased by double, resembling energies considered promising for Pharmaceutical lead compounds. This molecular docking strategy mimics the ligand fragment approach used in the Pharmaceutical Industry and reveals that readily available computational tools for dynamic evaluation allow identification and improvement of ligand binding.