Quantum mechanical/molecular mechanical (QM/MM) docking: an evaluation for known test systems

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Details zur Publikation

Autorinnen und Autoren: Beierlein F, Lanig H, Schürer G, Horn A, Clark T
Zeitschrift: Molecular Physics
Verlag: Taylor & Francis: STM, Behavioural Science and Public Health Titles / Taylor & Francis
Jahr der Veröffentlichung: 2003
Band: 101
Heftnummer: 15
Seitenbereich: 2469-2480
ISSN: 0026-8976


A combined quantum mechanical/molecular mechanical (QM/MM) docking approach for the investigation of protein-inhibitor complexes is presented. Starting points for QM/MM optimizations are generated with AutoDock. The subsequent semiempirical AM1 QM/MM optimization of the complex obtained by the docking procedure gives a more detailed description of the binding mode and the electronic properties of the ligand. As we use a flexible protein environment in the QM/MM optimizations, we are able to simulate limited structural changes of the enzyme upon binding a ligand, even within a simple geometry optimization. The method was validated using a set of structurally known protein-inhibitor complexes, whose crystallographic data were taken from the Protein Data Bank. In addition to protein structures taken directly from complexes with the inhibitors, structures of uncomplexed HIV-1-protease and thrombin were also used successfully for QM/MM docking experiments. By comparing the resulting structures with those obtained using protein structures from protein-inhibitor complexes, we find that the method is able to simulate the effect of the induced fit when a simple optimization is adequate to reproduce the protein movement. Describing the ligand quantum mechanically gives a detailed view of its electronic properties, for example its polarization within the active site of the enzyme. This study suggests strongly that a QM/MM molecular dynamics approach will be able to simulate the induced fit in general cases.

FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Beierlein, Frank Dr.
Clark, Timothy apl. Prof. Dr.
Horn, Anselm Dr.
Professur für Bioinformatik
Lanig, Harald PD Dr.
Exzellenz-Cluster Engineering of Advanced Materials


Beierlein, F., Lanig, H., Schürer, G., Horn, A., & Clark, T. (2003). Quantum mechanical/molecular mechanical (QM/MM) docking: an evaluation for known test systems. Molecular Physics, 101(15), 2469-2480. https://dx.doi.org/10.1080/0026897031000092940

Beierlein, Frank, et al. "Quantum mechanical/molecular mechanical (QM/MM) docking: an evaluation for known test systems." Molecular Physics 101.15 (2003): 2469-2480.


Zuletzt aktualisiert 2018-10-08 um 05:53