MARISETTI HEMANTHKUMAR*, AMINENI UMAMAHESWARI,DIBYABHABA PRADHAN AND MANNE MUNIKUMAR

ARS, ANGRAU, Perumallapalle-517 507, Chittoor Dt., A.P.

ABSTRACT

Inversion of sucrose, impairing sugar recovery from harvested sugarcane leads to reduction in sugar production. The inver-sion or sucrose catabolism in sugarcane stalks mostly is due to the enzymatic activity of soluble acid invertases. With an objec-tive to save sucrose from degradation to glucose and fructose, virtual screening, docking and molecular dynamics simulations were implemented to identify potential soluble acid invertase inhibitors. Soluble acid invertase 3D structure (PM0076107) was prepared in protein preparation wizard of Maestro v9.2. A set of 372 structural analogues of sucrose were obtained from one million compounds of ligand info Meta database. Ligands were prepared using LigPrep to generate fully customized ligand dataset of 2,520 conformations. Using Glide v5.7, the dataset was docked with in the active site of soluble acid invertase. Out of the docked ligands, 64 lead molecules with better XPGscore than sucrose were identified. The 15 leads selected based on clustering were re-docked through quantum polarized ligand docking. Based on results of the both docking protocols, 15 leads were proposed as potential inhibitors of soluble acid invertase. Lead 1, showed the best Gscore (XP: -12.07 kcal/mol; QPLD: -13.07 kcal/mol) and interactions with residues that are important for sucrose binding. Furthermore, Prime/MM-GBSA calcula-tion of soluble acid invertase-lead1 complex obtained after QPLD showed lowest free energy of ligand binding (“G = -166.02 kcal/mol). The conformational and interaction stability of soluble acid invertase – lead1 docking complex was stable during 10ns molecular dynamic simulations. Therefore, lead1 was proposed as potential competitive inhibitor to sucrose.

KEYWORDS:

Sugarcane, sucrose, soluble acid invertase inhibitors, virtual screening, molecular dynamics simulations.