Abstract
We performed a comprehensive structure validation of both automated and manually generated structures of the 10 targets of the CASD-NMR-2013 effort. We established that automated structure determination protocols are capable of reliably producing structures of comparable accuracy and quality to those generated by a skilled researcher, at least for small, single domain proteins such as the ten targets tested. The most robust results appear to be obtained when NOESY peak lists are used either as the primary input data or to augment chemical shift data without the need to manually filter such lists. A detailed analysis of the long-range NOE restraints generated by the different programs from the same data showed a surprisingly low degree of overlap. Additionally, we found that there was no significant correlation between the extent of the NOE restraint overlap and the accuracy of the structure. This result was surprising given the importance of NOE data in producing good quality structures. We suggest that this could be explained by the information redundancy present in NOEs between atoms contained within a fixed covalent network.Electronic supplementary materialThe online version of this article (doi:10.1007/s10858-015-9949-0) contains supplementary material, which is available to authorized users.
Highlights
In the CASD-NMR-2013 effort, 164 entries were submitted across ten targets
We established that automated structure determination protocols are capable of reliably producing structures of comparable accuracy and quality to those generated by a skilled researcher, at least for small, single domain proteins such as the ten targets tested
The ensemble convergence of each of the CASD-NMR2013 entries and target ensembles and the similarity of the entry to the corresponding target ensemble were assessed using the deviation of the backbone coordinates, expressed as the average of the pairwise root mean square deviation (RMSD) between the conformers in the reference and entry ensembles using the well-defined regions defined for the reference ensemble by CyRange (Kirchner and Guntert 2011)
Summary
In the CASD-NMR-2013 effort (see accompanying paper, Rosato et al 2015), 164 entries were submitted across ten targets. Together, these data provide for the opportunity to assess the current state of automated structure calculation methods for small- to medium-sized proteins. Some automated methods are even purely chemical-shift (CS) based (Shen et al 2008), requiring no additional data at all and. Whether derived by automated methods or manually, it is imperative that the result is accurate and properly reflects the underpinning data. An expert NMR validation task force (NMR-VTF) has published a set of recommendations for validating NMR-derived structures and accompanying experimental data (Montelione et al 2013)
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