DC+: A web server for the analysis of residual dipolar couplings

A server-based program, DC+, is presented for analysis of residual dipolar couplings (RDCs) and residual chemical shift anisotropy (RCSA) in proteins and nucleic acids. The program aims to meet commonly encountered needs in the analysis of RDCs. In addition to standard fitting of RDCs to known internuclear vector orientations using standard singular value decomposition (SVD), a multitude of features allow adjustment of such fits to specific cases: (1) fitting to the sum of RDCs, such as commonly measured for methylene or methyl ¹³C-¹H vectors, (2) fitting of RDCs to ensembles of structures, with either equal or optimized weights for the ensemble members, (3) fitting of RDCs to idealized α-helical or canonical nucleic-acid duplex structure, (4) orthogonalization of multiple sets of alignment tensors and generation of orthogonalized RDC sets, and (5) fitting of RCSA to either a static structure or an ensemble. The program includes options to weigh experimental RDCs by the inverse of their reported uncertainty, to select different sets of RDCs for validation from those used for fitting, and to carry out jackknifed cross-validation, a feature that is particularly useful when only few RDCs (< ∼25) are available. DC+ also contains a robust non-linear least-squares fitting mode, suitable for evaluation of data in cases where the magnitude and/or asymmetry of the alignment tensor are known. By integrating fitting, validation, uncertainty analysis, ensemble optimization, and visualization within a single web interface, DC+ provides a comprehensive environment for routine and advanced RDC analysis. The server is freely available at https://spin.niddk.nih.gov/bax-apps/nmrserver/dc+/.