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Updated: Apr 27, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Evaluation of interactions between urokinase plasminogen and inhibitors using molecular dynamic simulation and
Rongjian Sa1, Liang Fang, Mingdong Huang
1State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter , 155 Yangqiao Road West, Fuzhou, Fujian 350002, People's Republic of China.
Abstract:
The binding modes of urokinase-type plasminogen activator (uPA) with five inhibitors (1-(7-sulfonamidoisoquinolinyl) guanidine derivatives) were predicted based on molecular dynamic simulations. MM/PBSA free-energy calculations and MM/GBSA free-energy decomposition analyses were performed on the studied complexes. The calculated binding free energies are reasonably consistent with the experimental results. The free-energy decomposition analyses elucidate the different contributions of the energy of some favorable residues in the interactions between protein and ligand of each complex. The results indicate that the inhibitors mainly interact with the S1 pocket of uPA, wherein the hydrogen bonds and the interactions between guanidines and the corresponding residues play an important role. Moreover, hydrogen bond analyses show the water-mediated hydrogen-bond network near the S1 pocket between uPA, and the ligand probably leads to excellent selectivity of these inhibitors on uPA.
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