Appraising the Potency of Small Molecule Inhibitors and Their Graphene Surface-Mediated Organizational Attributes on Uric Acid-Melamine Clusters

Uric acid (UA) and melamine (MM) crystallization in humans are associated with adverse medical conditions, including the germination of kidney stones, because of their low solubility. The growth of kidney stone usually formed on renal papillary facades is accomplished on the matrix- coated surface by aggregating preformed crystals or secondary crystal nucleation. Therefore, the effects of inhibitors such as theobromine (TB) and allopurinol (AP) on the MM-UA aggregation are investigated by employing classical molecular dynamics simulation on the graphene surface. It impersonates the exact essence of precipitation of kidney stone. The interaction between MM-UA is very intense, thus forming a large cluster on the surface. The presence of TB and AP will, however, substantially inhibit their aggregation. TB and AP significantly impede UA aggregation in particular. Therefore, lower-order UA clusters are formed. Such smaller UA clusters then pull the lower number of MM towards themselves, resulting in a smaller order UA-MM cluster. MM and UA aggregation on a 2D surface is found to be spontaneous. There is no difference in these molecules’ adsorption with a change in graphene surface size and force field parameters (i.e., GAFF and OPLS-AA). The greater the surface area of graphene, the more molecules are absorbed. The solute-surface van der Waals interaction energy plays as driving force for solute molecules’ adsorption on the surface. Besides, interactions like hydrogen bonding and π-stacking over the graphene surface involve binding all like molecules. These aggregated solute molecules strongly attract more like molecules until all solute molecules are adsorbed on the graphene surface as estimated by the enhanced sampling. The molecular origin of graphene exfoliation by MM is also described here. The present work helps to design novel kidney stone inhibitors.