Multiscale Biomechanical Characterization From Molecular Dynamics To Locomotor Gait Kinematics: Ameliorative Effects Of Ganoderic Acid A On Motor Dysfunction In MPTP-Induced Parkinson'S Disease Mice

Parkinson’s disease (PD)-related motor dysfunction involves abnormalities across multiple biological scales, yet current pharmacological evaluations often assess molecular interactions and locomotor function separately. Here, we established a multiscale biomechanical characterization framework integrating network pharmacology-assisted target screening, molecular dynamics (MD) simulation, and whole-body gait kinematics, and used ganoderic acid A (GAA) as a model compound for validation. Network pharmacology identified 171 overlapping GAA-PD targets and eight core candidate targets, among which EGFR showed the most favorable predicted binding with GAA. A 100-ns MD simulation provided preliminary evidence of relatively stable conformational dynamics of the GAA-EGFR complex. In an MPTP-induced PD mouse model, GAA partially restored abnormalities in toe spread, stride length, and step width, accompanied by improved overall locomotor activity. These findings demonstrate the feasibility of integrating molecular conformational dynamics with whole-body gait kinematics for multiscale biomechanical evaluation of PD interventions. GAA served as a model compound supporting the applicability of this framework, while the molecular interaction between GAA and EGFR requires further experimental validation.