Structure-based computational prioritization of Emodin-8-glucoside as a candidate ligand for the VEGFR1 kinase domain in the context of placenta previa

Placenta previa is a serious obstetric condition associated with abnormal placental implantation and hemorrhagic complications, for which no targeted pharmacological therapy is established. This study applied an integrated structure-based computational workflow to explore the intracellular VEGFR1 kinase domain as a candidate molecular target. Twenty-one phytochemicals were screened using AutoDock Vina and MOE, with Emodin-8-glucoside consistently prioritized among the highest-ranked compounds. Redocking of the co-crystallized ligand 8ST reproduced its experimental pose with a heavy-atom RMSD of 1.465 Å. Comparative 500 ns molecular dynamics simulations showed persistent binding-site association of Emodin-8-glucoside and the 8ST control. End-point energy estimates were method dependent, with MM-GBSA yielding a negative mean estimate while MM-PBSA yielded a near-zero estimate with substantial variability. DFT analysis produced a HOMO-LUMO gap of 0.13204 Hartree (approximately 3.59 eV). SwissADME and ProTox 3.0 identified low gastrointestinal absorption, P-glycoprotein substrate behavior, high polarity, and several predicted toxicity liabilities. Overall, Emodin-8-glucoside represents an in-silico-prioritized exploratory candidate requiring biochemical, selectivity, placental-cell, and pregnancy-safety validation.