Protein ensemble generation

Protein Flexibility Analysis and Protein Ensemble Generation... 

V. I. Lesk and M. J. Sternberg, Bioinformatics, 24,1137-1144 (2008). 3D-Garden A System for Modelling Protein-Protein Complexes Based on Conformational Refinement of Ensembles Generated with the Marching Cubes Algorithm. 

Fig. 9. Two-dimensional sketch of the 3N-dimensional configuration space of a protein. Shown are two Cartesian coordinates, xi and X2, as well as two conformational coordinates (ci and C2), which have been derived by principle component analysis of an ensemble ( cloud of dots) generated by a conventional MD simulation, which approximates the configurational space density p in this region of configurational space. The width of the two Gaussians describe the size of the fluctuations along the configurational coordinates and are given by the eigenvalues Ai.

Step 1 A short conventional MD simulation (typically extending over a few lOOps) is performed to generate an ensemble of protein structures x 6 71 (each described by N atomic positions), which characterizes the initial conformational substate. The 2-dimensional sketch in Fig. 9 shows such an ensemble as a cloud of dots, each dot x representing one snapshot of the protein. 

Molecular dynamics (MD) should be performed for binding pockets defined mostly by side chains of flexible protein residues to generate an ensemble of binding sites. Such an ensemble can be used for subsequent docking or virtual screening in a parallel fashion. 

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