Sampling of conformation space in torsion angle dynamics calculations

Torsion angle dynamics (TAD) performs molecular dynamics simulation using torsion angles instead of Cartesian coordinates as degrees of freedom. TAD algorithms used in conjunction with simulated annealing are one of the common methods for the calculation of three-dimensional protein structures from NMR data. For this application of TAD, unbiased sampling of conformation space is essential. This paper presents a systematic study of the sampling of conformation space in protein structure calculations with the TAD algorithm implemented in the program Dyana, and compares the results with those obtained with a different TAD algorithm in the program CNS. Examples used are unconstrained poly-alanine peptides of length 20 to 100 residues, and the globular protein Antennapedia(C39S) homeodomain, which comprises unstructured polypeptide segments at the two chain termini and was calculated from a high-quality experimental NMR data set. The results show that the different implementations of TAD all have good sampling properties for calculating protein structures that are well-constrained by experimental NMR data. However, if TAD is used for studies of long unconstrained polypeptides, the results obtained in this paper show that the molecule needs to reorient freely in space, and that the total angular and linear momenta of the system are conserved and periodically reset to zero.

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