Molecular interactions/docking

The interpretation of molecular surfaces is particularly important wherever molecular interactions, reactions, and properties play a dominant role, such as in drug design or in docking c.xpcrimcnts. 

Schneidman-Duhovny D, Nussinov R and Wolfson HJ. Predicting molecular interactions in silico II. Protein-protein and protein-drug docking. Curr Med Chem 2004 11 91-107. 

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. 

Lewis, D. F., Lake, B. G., and Parke, D. V. (1995) Molecular orbital-generated QSARs in a homologous series of alkoxyresorufins and studies of their interactive docking with P450s. Xenobiotica 25, 1355-1369. 

Another difference between protein-protein and protein-small-molecule docking involves the treatment of nonbonded interactions. For the docking of rigid low molecular weight compounds, the receptor s molecular interaction... 

It is important to stress that the method highlighted here requires neither training nor docking procedures and associated scoring functions, nor 2D or 3D QSAR models. The only experimental information used as input is the 3D structure of the human cytochromes. From the 3D CYP structures, GRID provides all the flexible molecular interaction fields, which in turn form the basis of the remaining calculations. 

A. Imberty, K.D. Hardman, J.P. Carver and S. Perez, Molecular modelling of protein-carbohydrate interactions. Docking of monosaccharides in the binding site of concanavalin A. Glycobiology, 1 (1991)631. 

Molecular dynamics methods are primarily used for the refinement of structural models (Li et al., 1997) or the analysis of molecular interactions (Cappelli et al., 1996 Kothekar et al., 1998). In both cases the time scales to be simulated are within range of current computing technology. Another application area is the study of allosteric movements of proteins (Tanner et al., 1993). Molecular Dynamics approaches to protein-ligand docking are described in Chapter 7 of Volume I. 

Harpsoe K, Liljefors T, Balle T (2008) Prediction of the binding mode of biarylpropylsulfo-namide allosteric AMPA receptor modulators based on docking, GRID molecular interaction fields and 3D-QSAR analysis. J Mol Graph Model 26 874-883... 

Marcou G, Rognan D (2007) Optimizing fragment and scaffold docking by use of molecular interaction fingerprints. J Chem Inf Model 47 195-207... 

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