బయోకెమిస్ట్రీ & అనలిటికల్ బయోకెమిస్ట్రీ

నైరూప్య

Docking and Molecular Dynamic Simulations of Legionella pneumophila MurB Reductase for Potential Inhibitor Design

Vani Priyadarshini, Dibyabhaba Pradhan, Manne Munikumar, Amineni Umamaheswari, D Rajasekhar and PVLN Srinivasa Rao

Legionella pneumophila is the causative organism for Legionnaires’ disease, pneumonia and life-threatening prosthetic valve endocarditis. MurB reductase, one of the important enzymes for biosynthesis of peptidoglycan, a component of cell wall, was identified as common drug target against bacterial pathogens causing infective endocarditis including Legionella pneumophila . MurB reductase with FAD acts as a cofactor and catalyzes the NADPH-dependent reduction of UDP-N-acetylenolpyruvylglucosamine (UDP-GlcNAcEP) to UDP-N-acetylmuramic acid. In the present study, 360 structural analogs of FAD were docked to MurB reductase of Legionella pneumophila using sequential protocol of Glide v5.7 implemented in virtual screening workflow of Maestro v9.2. Among seven leads were obtained through docking analysis, only lead1 (XPGscore -13.27Kcal/mol) was observed to have better binding affinity towards MurB reductase as compared to cofactor FAD (XPGscore -13.25Kcal/mol). Molecular level interactions of the MurB reductase- lead1 docking complex showed good correlation with MurB reductase- FAD complex. Further, molecular dynamic simulations for MurB reductase - lead1 docking complex were performed using Desmond v3.0 to shed light on natural dynamic of the docking complex in solution on different timescales. Molecular dynamic simulations of MurB reductase - lead1 complex showed stable nature of the docking interactions.