Docking molecules

Recent results indicate that not only topogenic signals and membrane composition contribute to the proper topology of a membrane protein. The antimicrobial peptide nisin, produced by Lactococcus lactis, kills Gram-positive bacteria via pore formation, thus leading to the permeabilisation of the membrane. Nisin depends on the cell-wall precursor Lipid II, which functions as a docking molecule to support a perpendicular stable transmembrane orientation [43]. 

Su, A. I., Lorber, D. M., Weston, G. S., Baase, W. A., Mathews, B. W., and Shoichet, B. K. (2001) Docking molecules by families to increase the diversity of hits in database screens computational strategy and experimental evaluation. Proteins Struc. Func. Genet. 42, 279-293. 

Combined experimental and computational approach with 12 new imidazoles and triazole derivatives using Auto Dock to dock molecules in sterol 14a-demethylase followed by free energy of binding calculations... 

There are two ways to dock molecules manually using translation and rotation... 

The phenotype of mice deficient in IRS-1 indicated that other docking molecules and substrates must be involved in insulin signalling.34 IRS-1-deficient mice were stunted in their growth and had impaired glucose tolerance, but the absence of IRS-1 did not completely eliminate the response to insulin. The need for another IRS also became apparent from the phenotypes of mice carrying insulin receptor mutants. A more likely candidate as primary substrate of the insulin receptor is IRS-2. In contrast to mice deficient in IRS-1, mice that lack the insulin receptor substrate-2 gene are hj erglycaemic and... 

Program that addresses the problem of docking molecules to each other. It explores ways in which two molecules, such as a drug and an enzyme or protein receptor, might fit together... 

The conformational properties of valsartan have been analyzed both in solution and at the binding site of the ATI receptor. These studies revealed two low energy conformations of valsartan in solution, cis/trans around the amide bond in the ratio of approximately 40 60, while the majority of the docked molecules at the ATI receptor are bound in the trans conformation [15], A schematic presentation of some of the important interactions of valsartan with the ATI receptor is given in Fig. 5.1 [16],... 

The development of accurate scoring functions to identify and compare equilibrium structures of target/docking molecule complexes is a challenging and unsolved problem. A general scoring function is represented in Eq. (101) ... 

The soft docking model represents the target and docking molecules as a collection of cubes rather than spheres. This method combines aspects of surface complementarity, grid search, and soft potential modeling. The cubic representation along with a grid search makes the translational and rotational searches much more efficient. In addition, the cubes implicitly allow for some volume overlap, which can be used in combination with surface complementarity to screen docked complexes [208]. 

Figure 20 Interfacial surface between trial docking of rtem (beta lactamase) and blip (beta lactamase inhibitory protein). Molecular surfaces are low order spherical harmonic. " Interfiacial surface is computed interactively on-the-fly while docking molecules are moved relative to each other. Color coding on molecular surfaces indicate shape properties. (Image courtesy of Arthur J. Olson, The Scripps Research Institute, La Jolla, CA)...

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