Conformation ensemble analysis

To extract the conformational properties of the molecule that is being studied, the conformational ensemble that was sampled and optimized must be analyzed. The analysis may focus on global properties, attempting to characterize features such as overall flexibility or to identify common trends in the conformation set. Alternatively, it may be used to identify a smaller subset of characteristic low energy conformations, which may be used to direct future drug development efforts. It should be stressed that the different conformational analysis tools can be applied to any collection of molecular conformations. These... 

Figure 6 (A) Scheme of the MUMO calculations used for calculating the dynamic conformation ensemble of SGCI. (B) Dynamic conformational ensemble of SGCI with the protease binding loop shown in dark grey. (C) Result of the principal component analysis on the inhibitor structures depicting that the dynamic conformational ensemble (blue circles) contains the conformers of corresponding to the enzyme-bound state (red boxes).

Table I presents the detailed packing geometries for ensembles consisting of up to two independently orientable chains of like conformation. Although analysis by simulation suggests several distinguishable candidates of comparable energy for chain packing in the oriented PPTA solid state, the predominant trends in structure formation may be deduced from the common elements across the set of packed geometries. The...

A. Mujeeb, N. B. Ulyanov, T. M. Billed, S. Farr-Jones and T. L. James, Conformational Ensemble Calculations Analysis of Protein and Nucleic Acid NMR Data , p. 201... 

Conformational Ensemble Calculations Analysis of Protein and Nucleic Acid NMR Data... 

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.

Obtaining an Ensemble of Conformations What is Conformational Analysis ... 

Other methods which are applied to conformational analysis and to generating multiple conformations and which can be regarded as random or stochastic techniques, since they explore the conformational space in a non-deterministic fashion, arc genetic algorithms (GA) [137, 1381 simulation methods, such as molecular dynamics (MD) and Monte Carlo (MC) simulations 1139], as well as simulated annealing [140], All of those approaches and their application to generate ensembles of conformations arc discussed in Chapter II, Section 7.2 in the Handbook. 

Hopfinger et al. [53, 54] have constructed 3D-QSAR models with the 4D-QSAR analysis formahsm. This formalism allows both conformational flexibility and freedom of alignment by ensemble averaging, i.e., the fourth dimension is the dimension of ensemble sampling. The 4D-QSAR analysis can be seen as the evolution of Molecular Shape Analysis [55, 56]. 

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