In silico profiling of date palm pollen phytochemicals: Molecular interactions with sperm-associated proteins and implications for male fertility

Background Male infertility is a significant global health concern, with sperm motility, morphology, and capacitation being critical determinants of reproductive success. Phoenix dactylifera pollen has been used in traditional medicine to support male fertility, but its molecular mechanisms remain poorly defined. Aim This study aimed to elucidate the molecular interactions between dominant phytochemicals from date palm pollen and key sperm-associated proteins through a comprehensive in silico approach. Methods Four major phytochemicals—catechin, gallic acid, quercetin, and rutin—were selected based on concentration (>2%) and reported pharmacological relevance. Fifteen sperm-associated proteins implicated in motility, morphology, and capacitation were modeled using GalaxyTBM, Phyre2, and SWISS-MODEL, followed by structural refinement (GalaxyRefine) and validation (ERRAT, PROCHECK, Verify3D, WHAT_CHECK). Molecular docking was performed with CB-Dock2, while protein flexibility and stability were assessed by Normal Mode Analysis and Atomic Displacement Parameter analysis. Pharmacokinetic and toxicity profiles were predicted using ADMETlab 2.0. Summary Catechin, quercetin, and gallic acid satisfied Lipinski's Rule of Five, indicating good oral bioavailability, while rutin demonstrated strong binding affinity but failed drug-likeness criteria. Rutin and quercetin exhibited the highest binding affinities with Catsper1 (−9.2 kcal/mol) and Catsper2 (−8.5 kcal/mol), respectively. These findings provide mechanistic evidence supporting the traditional use of date palm pollen in enhancing male fertility and highlight its potential as a phytotherapeutic candidate. However, this study is limited to computational approaches, and further validation through in vitro and in vivo studies is required to confirm the biological relevance of these findings.