Using Experimental Data as Restraints

You can often use experimental data, such as Nuclear Overhauser Effect (NOE) signals from 2D NMR studies, as restraints. NOE signals give distances between pairs of hydrogens in a molecule. Use these distances to limit distances during a molecular mechanics geometry optimization or molecular dynamics calculation. Information on dihedral angles, deduced from NMR, can also limit a conformational search. 

When using NOE signals as restraints, choose the distance between the nonbonded atoms. A typical distance is about 4 to 5 Angstroms. Atypical force constant is 0.5 to 5.0 kcal/A, depending on the flexibility of the rest of the molecule and the strength of the NOE signal. 

You usually remove restraints during the final phases of molecular dynamics simulations and geometry optimizations. 

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Restrained or biased simulations, mentioned previously, can be used to generate ensembles of structures consistent with transition states using experimental data as restraints. In these cases, identification of the transition states is a straightforward outcome of the simulation. Conformations that have reached the restrained target experimental values, such as O-values, are selected as members of the When using other approaches,... 

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