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Improvement of hydrogen bond geometry in protein NMR structures by residual dipolar couplings – an assessment of the interrelation of NMR restraints

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Abstract

We have examined how the hydrogen bond geometry in three different proteins is affected when structural restraints based on measurements of residual dipolar couplings are included in the structure calculations. The study shows, that including restraints based solely on 1HN-15N residual dipolar couplings has pronounced impact on the backbone rmsd and Ramachandran plot but does not improve the hydrogen bond geometry. In the case of chymotrypsin inhibitor 2 the addition of 13CO-13Cα and 15N-13CO one bond dipolar couplings as restraints in the structure calculations improved the hydrogen bond geometry to a quality comparable to that obtained in the 1.8 Å resolution X-ray structure of this protein. A systematic restraint study was performed, in which four types of restraints, residual dipolar couplings, hydrogen bonds, TALOS angles and NOEs, were allowed in two states. This study revealed the importance of using several types of residual dipolar couplings to get good hydrogen bond geometry. The study also showed that using a small set of NOEs derived only from the amide protons, together with a full set of residual dipolar couplings resulted in structures of very high quality. When reducing the NOE set, it is mainly the side-chain to side-chain NOEs that are removed. Despite of this the effect on the side-chain packing is very small when a reduced NOE set is used, which implies that the over all fold of a protein structure is mainly determined by correct folding of the backbone.

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Author notes

  1. Mathilde Hauge Lerche

    Present address: Amersham Health, P. A. Hanssons V 41, S-205 12, Malmö, Sweden

Authors and Affiliations

  1. Institute of Molecular Biology, University of Copenhagen, Øster Farimagsgade 2A, DK-1353, Copenhagen K., Denmark

    Pernille Rose Jensen, Jacob Bock Axelsen, Mathilde Hauge Lerche & Flemming M. Poulsen

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  1. Pernille Rose Jensen
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  2. Jacob Bock Axelsen
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  3. Mathilde Hauge Lerche
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  4. Flemming M. Poulsen
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Correspondence to Flemming M. Poulsen.

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Jensen, P.R., Axelsen, J.B., Lerche, M.H. et al. Improvement of hydrogen bond geometry in protein NMR structures by residual dipolar couplings – an assessment of the interrelation of NMR restraints. J Biomol NMR 28, 31–41 (2004). https://doi.org/10.1023/B:JNMR.0000012865.35872.cc

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