In Silico Identification of MyD88 Pathway Modulator and the Impact of Anesthesia Protocols in Pediatric OSAHS with Allergic Rhinitis: A Computer-Aided Drug Design and Clinical Evaluation Study

Pediatric obstructive sleep apnea hypopnea syndrome (OSAHS) with allergic rhinitis involves airway obstruction and an inflammatory milieu that current symptomatic therapies do not fully address. We integrated de novo design and AI-guided fragmentation with docking and long-timescale molecular dynamics (MD) to identify small-molecule modulators of the MyD88 pathway, and in parallel conducted a clinical evaluation of anesthesia protocols and their impact on oral–respiratory microbiota in children with OSAHS. Among three de novo ligands and twenty AI-optimized analogs, AI-Fragmented Drug 1 showed the best docking score (–7.0 kcal/mol) against the MyD88 TIR domain and, over 500 ns MD, maintained a low-variance ligand RMSD (0.4–0.6 Å) and stable protein backbone, with persistent hydrogen bonds to LYS250/THR272/LEU252 and hydrophobic contacts with CYS274/ARG288/ALA292. Conformational analyses (DCCM and PCA) indicated damped interface-centered motions and convergence into restricted basins, consistent with a single, well-stabilized pose. MM-GBSA yielded a strongly favorable ΔG_bind of –41.87 kcal/mol dominated by lipophilic and non-polar solvation terms, aligning with the observed contact network; in-silico ADMET suggested high gastrointestinal absorption and overall drug-like features. Clinically, in 80 pediatric patients randomized to four perioperative dexmedetomidine/anesthesia regimens, the intravenous pretreatment plus intravenous maintenance group showed the most stable hemodynamics and the highest microbial diversity, whereas higher-dose nasal instillation arms were associated with compositional shifts in bacterial richness. Collectively, these computational and clinical findings nominate AI-Fragmented Drug 1 as a lead MyD88 modulator for preclinical validation and suggest anesthesia protocol selection may mitigate perioperative instability and microbiome perturbation in pediatric OSAHS.