Restraints/restrained molecular dynamics

In a related way, ensemble molecular dynamics derives a pharmacophore using restrained molecular dynamics for a collection of molecules. A force field model is set up so that none of the atoms in each molecule sees the atoms in ainy other molecule. This enables the molecules to be overlaid in space. A restraint term is included in the potential, which forces the appropriate atoms or functional groups to be overlaid in space. 

If all nuclei are assigned and the spectral parameters for the conformational analysis are extracted, a conformation is calculated - usually by distance geometry (DG) or restrained molecular dynamics calculations (rMD). A test for the quality of the conformation, obtained using the experimental restraints, is its stability in a free MD run, i.e. an MD without experimental restraints. In this case, explicit solvents have to be used in the MD calculation. An indication of more than one conformation in fast equilibrium can be found if only parts of the final structure are in agreement with experimental data [3]. Relaxation data and heteronuclear NOEs can also be used to elucidate internal dynamics, but this is beyond the scope of this article. 

The most definitive proof of p-sheet structure requires the determination of the three-dimensional solution structure of the peptide. For the calculation of such structures one requires the accurate determination of coupling constants by DQF-COSY experiments which give backbone dihedral restraints and through-space connectivities (ROESY or NOESY experiments) which give rise to distance restraints. A combination of these restraints allows the calculation of the three-dimensional structure of the peptide using restrained molecular dynamics simulations. Utilizing this methodology, the three-dimensional structures of a number of cyclic peptides have been solved.[411... 

D. Bassolino-Klimas, R. Tejero, S. R. Krystek, W. J. Metzler, G. T. Montelione, R. E. Bruccoleri. Simulated annealing with restrained molecular dynamics using a flexible restraint potential theory and evaluation with simulated NMR constraints. Protein Sci. 1996, 5, 593-603. 

You can include geometric restraints—for interatomic distances, bond angles, and torsion angles—in any molecular dynamics calculation or geometry optim i/.ation. Here are some applications of restrain ts ... 

The default restraints are appropriate for molecular dynamics calculations where larger force constants would create undesirable high frequency motions but much larger force constants may be desired for restrained geometry optimization. 

Recent developments in molecular dynamics techniques allow consideration of values and NOE restraints as an ensemble property (Lindorff-Larsen et al. 2005 Richter et al. 2007). The obtained ensembles represent a more realistic view of these flexible molecules in solution than those calculated with conventional NMR structure refinement methods. The dynamically restrained ensembles occupy a considerably larger conformational space than the conventionally calculated ones, and reproduce independent NMR parameters (e.g., chemical shifts) much better. 

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