Lead generation of UPPS inhibitors targeting MRSA: Using 3D-QSAR pharmacophore modeling, virtual screening, molecular docking, and molecular dynamic simulations.

ABSTRACT: Undecaprenyl Pyrophosphate Synthase (UPPS) is a vital target enzyme in the early stages of bacterial cell wall biosynthesis. UPPS inhibitors have antibacterial activity against resistant strains such as MRSA and VRE. In this study, we used several consecutive computer-based protocols to identify novel UPPS inhibitors. The 3D QSAR pharmacophore model generation (HypoGen algorithm) protocol was used to generate a valid predictive pharmacophore model using a set of UPPS inhibitors with known reported activity. The developed model consists of four pharmacophoric features: one hydrogen bond acceptor, two hydrophobic, and one aromatic ring. It had a correlation coefficient of 0.86 and a null cost difference of 191.39, reflecting its high predictive power. Hypo1 was proven to be statistically sig

SUBMITTER: Qandeel BM 

PROVIDER: S-EPMC10800075 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature