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| Molecular dynamics simulation on the molecular interactions of peptide deformylase and actinonin |
| GAO Jian WANG Tao SUN Jie MOU Jie |
| Xuzhou Medical College Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Jiangsu Province, Xuzhou 221004, China |
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Abstract [Abstract] Objective To investigate the binding modes between actinonin and peptide deformylases and to characterize the informations about how to design the specific HsPDF inhibitor. Methods The combination of molecular dynamics simulation and MM/GBSA free energy calculation was employed to study the interactions between several PDF enzymes and actinonin. The detailed interactions of each residues of protein and actinonin were calculated by MM/GBSA free energy decomposition. Results Three important differences in actinonin binding to PDFs were obtained as followed: actinonin had stronger binding interaction with the motif 1 of HsPDF than the motif 2, while actinonin had lower binding interaction with the motif 1 than the motif 2 for PDF1A and PDF2. Moreover, actinonin had stronger binding affinities with Leu131 and Met145 of HsPDF, but had no interaction with the corresponding ones of PDF1A and PDF2. In addition, actinonin interacted strongly with Trp207 of HsPDF but weakly with the corresponding residue of PDF1A and PDF2. Conclusion By using the method of molecular dynamics simulation, the interaction of actinonin and PDF model are studied, differences of HsPDF and PDF in the active site with other types are expounded, based on the design thinking of specific HsPDF inhibitors of actinonin is proposed.
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