Integrated Computational Pipeline for the Identification of Novel PARP-1 Inhibitors: Hybrid Virtual Screening and Molecular Dynamics Simulations

Abstract Despite the promising anticancer properties of PARP-1 inhibitors, their clinical use is hindered by side effects. It is crucial to explore new structural variants of these inhibitors to increase efficacy and minimize side effects, enhancing their clinical viability and therapeutic scope. In this study, we developed a virtual screening workflow that synergistically integrates Transfoxmol, KarmaDock, and PLANET with AutoDock Vina's capabilities. Through structural clustering, we identified ten potential PARP-1 inhibitors. Additionally, through molecular dynamics simulations and MM/PBSA, we elucidated the binding modes of compounds 1, 3, 6, and 9 with PARP-1, providing insights for drug development.