Molecular dynamics simulation techniques for determination of molecular structures from nuclear magnetic resonance data

This chapter discusses the molecular dynamics (MD) simulation techniques for determination of molecular structures from nuclear magnetic resonance (NMR) data. This chapter presents with a short description of the MD technique and explain how the force field can be modified in order to bring or keep protons close together when a NOE between them has been measured. The combined use of distance geometry calculations and distance bounds driven dynamics gives insight into the accuracy of structure determinations by NMR. Refinement by restrained molecular dynamics improves the quality of the structures in terms of energetics. It is important in this respect to discriminate between uncertainties in the structure determination and thermal fluctuations. Computer simulation of at least the high-frequency modes of a molecule's thermal motions by MD and calculation of the experimentally observed parameters by proper averaging over computed trajectories can be used to support a dynamic model, in which more than one “dynamic conformation” may have to be included to explain all experimental results