Substrate docking

Zhu, D., Yang, Y., Buynak, J.D. and Hua, L. (2006) Stereoselective ketone reduction by a carbonyl reductase from Sporobolomyces salmonicolor. Substrate specificity, enantioselectivity and enzyme—substrate docking studies. Organic and Biomolecular Chemistry, 4 (14), 2690-2695. 

The modular architecture of RNA structure lends some support to the assumption that adding duplexes at the ends of the molecule will not generally perturb its behavior (Brion and Westhof, 1997 Tinoco and Bustamante, 1999). Single molecule studies demonstrated that the overall folding rate, substrate docking rate and catalysis by the Tetrahymena group I... 

DeVoss JJ, Sibbesen O, Zhang ZP, et al. Substrate docking algorithms and prediction of the substrate specificity of cytochrome P450(cam) and its L244A mutant. J Am Chem Soc 1997 119 5489-5498. 

Maves, S. A.,Yeom, H., Mclean, M. A., and Sligar, S. G., 1997, Decreased substrate affinity upon alteration of the substrate-docking region in cytochrome P450 BM3, FEBS Lett. 414 2136218. 

Figure 4 Chemical tools for the study of y-secretase. Transition-state anaiog inhibitors inciude hydroxyi-containing moieties that interact with the catalytic aspartates of aspartyl proteases. Helical peptides mimic the APR transmembrane domain and interact with the substrate docking site on the protease. These potent inhibitors were converted into affinity labeling reagents that contain a chemicaiiy reactive bromoacetyi or photoreactive benzophenone for covalent attachment to the protein target and a biotin moiety to allow isolation and detection of the labeled protein. Both types of chemical probes interacted with the two presenilin subunits but at distinct locations, which suggests that both the active site and the docking site of y-secretase lie at the interface between these subunits.

Figure 6. Stereo diagram of the substrate binding domain using the substrate docking method.

Occlusion substrate-binding channel Providing substrate-docking sites... 

The paradox concerning the generation of opposite enantiomers in the hydrogenation of N- 1 -phenylvinyl)acetamide and N-( 1 - -butylvinyl)acetamide with 104 is now understood on the grounds that the mode of substrate docking at the migratory insertion step of the catalytic cycle determines the stereochemical outcome. -... 

This chapter describes computational strategies for investigating the species in the catalytic cycle of the enzyme cjdochrome P450, and the mechanisms of its main processes alkane hydroxylation, alkene epoxidation, arene hydroxylation, and sulfoxidation. The methods reviewed are molecular mechanical (MM)-based approaches (used e.g., to study substrate docking), quantum mechanical (QM) and QM/MM calculations (used to study electronic structure and mechanism). 

For an MD approach with QM/MM design a protocol (preequilibration with a classical force field, substrate docking, boundary conditions, number and length of sampling windows, etc.). 

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