Flexible superposition

Klebe, G., Mietzner, T., Weber, F. Methodological developments and strategies for a fast flexible superposition of drug-size molecules. J. Comput.-Aided Mol. Des. 1999, 13, 35 9. 

Lemmen, C. and Lengauer, T. Time-efficient flexible superposition of medium-sized molecules./. Comput Aided Mol. Des. 1997, 3 3, 357-368. 

Fig. 8. (a) Structure of the full-length Rieske protein from bovine heart mitochondrial bci complex. The catalytic domain is connected to the transmembrane helix by a flexible linker, (b) Superposition of the three positional states of the catalytic domain of the Rieske protein observed in different crystal forms. The ci state is shown in white, the intermediate state in gray, and the b state in black. Cytochrome b consists of eight transmembrane helices and contains two heme centers, heme and Sh-Cytochrome c i has a water-soluble catalytic domain containing heme c i and is anchored by a C-terminal transmembrane helix. The heme groups are shown as wireframes, the iron atoms as well as the Rieske cluster in the three states as space-filling representations. 

Mills JEJ, De Esch IJP, Perkins TDJ, Dean PM. SLATE a method for the superposition of flexible ligands. J Corn-put Aided Mol Design 2001 15 81-96. 

Virtual screening applications based on superposition or docking usually contain difficult-to-solve optimization problems with a mixed combinatorial and numerical flavor. The combinatorial aspect results from discrete models of conformational flexibility and molecular interactions. The numerical aspect results from describing the relative orientation of two objects, either two superimposed molecules or a ligand with respect to a protein in docking calculations. Problems of this kind are in most cases hard to solve optimally with reasonable compute resources. Sometimes, the combinatorial and the numerical part of such a problem can be separated and independently solved. For example, several virtual screening tools enumerate the conformational space of a molecule in order to address a major combinatorial part of the problem independently (see for example [199]). Alternatively, heuristic search techniques are used to tackle the problem as a whole. Some of them will be covered in this section. 

Lemmen, C., Lengauer, T., and Klebe, G. ELEXS a method for fast flexible ligand superposition./. Med. Chem. 1998, 41, 4502-4520. 

Streich, W.J. DIGFIT a superposition generator for flexible molecules. In Trends in QSAR and Molecular Modelling 92, Wermuth, C.G. (Ed.J. Kluwer, Leiden, 1992, 416-417. 

The superposition of the molecules is often rather subjective and it takes hardly into account the flexibility of the molecules studied. 

Handschuh, S., Wagener, M., and Gasteiger, J. (1998) Superposition of three-dimensional chemical structures allowing the conformational flexibility by a hybrid method../. Chem. Inf. Comput. Sci. 38, 220-232. 

Lemmen C, Lengauer T, Klebe G (1998) FlexS A method for flexible ligand superposition. J Med Chem 41 4502-4520... 

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