Dynamic docking model

The same method has been applied to measure the Eli domain orientation when the protein is in complex with its RNA parmer or both RNA and thiostrepton antibiotic. The additional RDCs revealed a rearrangement of the N-terminal domain of Ell placing it closer to the RNA after binding of thiostrepton. HADDOCK has been used to calculate a model of the ternary stmcture of the Ell protein in complex with RNA and antibiotic. Based on the orientational data, the dynamics and the docking model, it seems that thiostrepton locks the domain conformation of Ell in a rigid (inhibitory) state. The antibiotic thiostrepton interferes with the interaction of elongation factors to this Ell-RNA region, which has a dramatic effect on the level of protein synthesis by the ribosome. 

Known III. Develop pharmacophore models and hypotheses, perform database searching, similarity searching, QSAR IV. Perform structure-based drug design, receptor-ligand interactions and dynamics, docking... 

Barhelt C, Schmid RD, Pleiss J. Regioselectivity of CYP2B6 homology modeling, molecnlar dynamics simnlation, docking. J Mol Model 2002 8 327-35. 

The Guy open conformation model docked structure was minimized in vacuo followed by a 1-ns molecular dynamics simulation of the complex embedded in a phosphatidylethanolamine (POPE) lipid bilayer. Adjustments were made to the model, and simulations were repeated so that very little movement occurred during the hnal iterations. Similar methods were used to dock the two domains in transitional and resting states. However, these results are more tenuous as little experimental data is available. In particular, the position of the S4-S5 linker and its role in opening and closing the pore are uncertain. The supplemental movie accompanying reference 36 illustrates the open-to-close-to-open cycle resulting from the simulations. 

Wang, D.-F., Helquist, P., Wiech, N.L. and Wiest, O. (2005) Toward selective histone deacetylase inhihitor design homology modeling, docking studies, and molecular dynamics simulations of human class I histone deacetylases. Journal of Medicinal Chemistry, 48, 6936-6947. 

Bathelt, C., Schmid, R. D., and Pleiss, J. (2002) Regioselectivity of CYP2B6 homology modeling, molecular dynamics simulation, docking. J. Mol. Model. 8, 327-35. 

Park, J. and Harris, D. (2003) Construction and assessment of models of CYP2E1 predictions of metabolism from docking, molecular dynamics, and density functional calculations. J. Med. Chem. 46, 1645-1660. 

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