Pocket flexibility

Nilmeier, J., Jacobson, M. Multiscale Monte Carlo sampling of protein sidechains application to binding pocket flexibility. J. Chem. Theory Comput. 2008, 4, 835-46. 

We further observe that it is possible to obtain low nanomolar inhibition without making the canonical benzamidine hydrogen bonds (Fig. 7.9). For a detailed discussion of non-canonical needles and recognition pocket and P pocket flexibility, the reader should consult ]41, 42, 45]. 

In order to study the effect of considering different bounds on N and C coordinates, the proposed approach was applied to all the pockets for 0.5 and 0.3 A bounds around the coordinates of the corresponding atoms of HLA-DRl molecule. The results are shown in Table XL. As was found from the crystallographic data of the I- molecule binding with different peptides (i.e., a peptide derived from murine hemoglobin Hb(64—76), or a peptide from murine heat shock protein 70 Hsp(236-248)), there is some inherent variability in the range of 0.01-0.4 A for N and C coordinates. These differences correspond to pocket flexibility to accommodate different peptides. 

More flexibility can be obtained with a variable volume clearance pocket such as that shown in Figure 11-20. This is a plug built into the outer cylinder head. When moved, the clearance volume of the outer end of the cylinder changes. 

Filled polyethylene separators are the only pocket material that has been able to meet all requirements of a starter battery reliably [39-48]. It is flexible and weldable into three-sided closed pockets, making the previously usual mud room at the bottom... 

Automatic flexible docking of molecules into the binding pocket, e.g., in order to study structure-activity/selectivity relationships... 

Muscimol and 4-PIOL are assumed to bind to the same binding site, but a direct superimposition of the amino groups and the 3-isoxazolol rings, which make up the pharmacophore elements in these compounds, seems impossible. However, owing to the flexibility of the arginine, this side chain can adopt an extended as well as a bent conformation, which makes it feasible to accommodate muscimol and 4-PIOL in the same binding pocket as illustrated in Fig. 6A. 

A., Gustafsson, J.A. and Carlquist, M. (2003) The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands. The Journal of Biological Chemistry, 278, 38821-38828. 

We have shown that the conformational behavior of natural aminoglycosides is characterized by a remarkable flexibility, with different conformations, even non-exo-anomeric ones, in fast exchange. This feature allows the adaptation of these ligands to the spatial and electronic requirements of the different receptors. The large diversity of structures adopted by aminoglycosides in the binding pocket of the different RNA receptors and the enzymes involved in bacterial resistance is consistent with this view. 

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