Docking conformational selection

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)... 

Subramanian G, Paterlini MG, Farson DF, Portoghese PS, Ferguson DM (1998) Conformational analysis and automated receptor docking of selective arylacetamide-based K-opioid agonists. J Med Chem 41 4777 -789... 

This simple example illustrates that the selection of the protein structure and also the explicit or implicit treatment of protein flexibility can have a large impact on docking results. Selecting a single receptor structure based on the assumption that all ligands bind to the same protein conformation can be misleading as observed for protein structure IqSu. A priori it is usually unknown which single protein structure... 

Approaches for fully flexible docking either follow a conformational selection or an induced fit concept (Figure 8.3). Ensemble docking implements the principle of conformational selection and relies on the protein structural change occurring before the ligand binds to the protein. The ensemble of input protein conformations... 

Parallel docking to multiple conformations selected from the trajectory is frequently used in combination with MD simulations. The periodic extraction of snapshots from an MD simulation is a straightforward way to select mrrltiple conformations. Subsequenfly, molecular docking is performed on the individual snapshots independently from each other. The continuoirs and unbiased selection should ideally represent the state space sampled in the simulatioa hr consequence, the resulting collection of snapshots represents a vahd thermodynamic ensemble and the subsequent ensemble of docking results are interpreted via statistical thermodynamics (see Sect. 15.2.2.3). 

Chaudhury S, Gray JJ (2008) Conformer selection and induced fit in flexible backbone protein-protein docking using computational and NMR ensembles. J Mol Biol 381(4) 1068-1087. doi 10.1016/j.jmb.2008.05.042... 

TrelletM, MelquiondA, Bonvin A (2013) Aunified conformational selection and induced fit approach to protein-peptide docking. PLoS One 8 e58769... 

S. Chaudhury and J. J. Gray,/. Mol. Biol., 381,1068-1087 (2008). Conformer Selection and Induced Fit in Flexible Backbone Protein-Protein Docking using Computational and NMR... 

Genetic algorithms can also be used to perform molecular docking [Judson et d. 1994 Jont et d. 1995b Oshiro et d. 1995]. Each chromosome codes not only for the internal conform tion of the ligand as described in Section 9.9.1 but also for the orientation of the ligand withi the receptor site. Both the orientation and the internal conformation will thus vary as th populations evolve. The score of each docked structure within the site acts as the fitnes function used to select the individuals for the next iteration. 

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