Fundamental and practical aspects of molecular dynamics using tensorial orientational constraints

Residual Dipolar Couplings are important structural parameters in high resolution NMR spectroscopy that allow the determination of configuration and conformation of small-to-medium-sized molecules even in difficult cases. The data interpretation for flexible molecules, however, is demanding and several downfalls are associated with established methods. With the Molecular Dynamics using Orientational tensorial Constraints (MDOC) approach, only recently a promising method for interpreting RDCs has been reported. Here, a fundamental derivation of the key equations of MDOC and the most commonly used alignment tensor concept is given, highlighting the profound differences of the two approaches. Next to the mathematical derivation, also the validity of resulting structural and orientational ensembles, the setting of important simulation parameters, the specific effect of tensorial constraints, and the nature of the expected outcomes are discussed in detail.