Docked conformations

Figure 14-11. Snapshots from the conformational switch path explored in the vicinity of the active conformation (unfolded docked conformation) and starting from the inactive (undocked) conformation found in crystal. Stems A and B were aligned (best fitted) and are shown in yellow, different instances of stem C are shown in stick representation with different colors. A schematic of the non-canonical binding scheme of the ligation site is shown in the right panel and the general mechanism of ligation in the left panel...

Zhou, Z., Madura, J.D. 3D QSAR Analysis of HIV-1 RT Nonnucleoside Inhibitors, TIBO Derivatives Based on Docking Conformation and Alignment. /. Chem. Inf Comput. Sci. 2004, 44, 2167-2178. 

The analysis and interpretation of docking results can be both difficult and time-consuming. When one is working with only a limited number of ligand molecules, visual analysis of the found docking conformations is still feasible. However, in the screening of large databases, this is hardly an option. The fact... 

File (in spreadsheet) > Put Rows into Molecule Areas Alternatively, if one has access to the CSCORE module of SYBYL, one can calculate scores of FlexX (50), Gold (38), PMF (51), Dock (52), and Chem-score (53) with a previously saved table of docked conformations. First, the table (corresponding to the database containing the conformations) is loaded File > Molecular Spreadsheet > New > Database (and select the database)... 

Deoxythymidine monophosphate derivatives that inhibit thymidine monophosphate kinase 36 MFA Alignments performed with least-squares (predictive R2=0.70), pharmacophore (0.56), or docked conformations (0.72). Receptor-based alignment performed best Aparna et al. (42)... 

Figure 8 Crystal structure of BANA113 bound to influenza virus neuraminidase. Docked conformations ranking first (correct) and eleventh (incorrect) in a DOCK/PMF score docking experiment are compared to the crystallographic binding mode.

Figure 4 The frequency of predicting the crystal structure of the SB203386-HIV-1 protease complex in docking simulations with the ensemble of 6 protein conformations (a). The RMSD of the docked inhibitor conformations from the crystal structure ranked by energy in simulations with the ensemble of 6 protein conformations (b) The energy distribution histogram of the docked conformations (c). The filled histogram (d) reflects the energies of the minimized crystal structures for 1) Isbg, 2) Ibdl, 3) Ibdq), 4) Ibdr, 5) Itcx, 6) Itcw protein structures. The standard AMBER energy function is used.

Prod-D-UF product in the docked conformation-forced unfolding... 

Prec-D-XTP reactant precursor in the docked conformation and the triphosphate in extended conformation... 

Both U38 and U19 are of particular interest in the current work U38 contributes to the docking of stem C into stem A in the active conformation and mutation data demonstrates that it is critical for catalysis, and U19 is evolutiona-rily conserved (97%), although its role in catalysis remains unclear [55,61-63]. In both crystallographic conformers, U19 is oriented toward the exterior of the L1L body without making any contacts. The lack of clear structural basis that explains the conserved character of U19 in either the docked or undocked crystal structures motivates the question as to whether this residue might be important in facilitating the undocked to docked conformational switch. 

A possible connection can be made between these relatively large fluctuations of some of the virtual torsions that span the junction region and the transition from the inactive to the active conformation. For example, during Prod-U simulation (370 ns), 01H is observed to transition through a series of two relatively distant clusters that are disposed exactly on the same path that would allow the undocked docked conformational transformation to occur as apparent from the crystal structure. 

The fact that U38, a conserved residue critical for catalytic activity in the L1L family, is docked into the ligation site and makes a canonical base pair with a constituent of the ligation site A51 in the docked conformation, whereas in the undocked conformation it is positioned 40 A away from the site, has led to the postulate that the former is more likely representative of a catalytically active state [64]. 

Lambert MH. Docking conformationally flexible molecules into protein binding sites. In Practical application of computer-aided drug design. New York Dekker, 1997. p. 243-303. 

This allowed the treatment of cyclic groups as rigid bodies. The total number of docked conformers was 1.7 million. 

Figure 9. Most favorable docked conformations obtained for each synthetic oligolignol over the cellulose l-fi macromolecular model. The H-bonds are represented with blue dashed hues. Pictures in the first column display the oligolignol-cellulose complex after the docking calculation, whereas pictures in the second column display a close-up view of the H-bonds formed.

Keywords Docking Conformation Stracture-based drag design Pharmacophore... 

Fig. 4.49 The docked conformations ofisoniazid in the active site in Autodock...

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