TY  - JOUR
A1  - Trautwein, Matthias
A1  - Fredriksson, Kai
A1  - Möller, Heiko Michael
A1  - Exner, Thomas E.
T1  - Automated assignment of NMR chemical shifts based on a known structure and 4D spectra
JF  - Journal of biomolecular NMR
N2  - Apart from their central role during 3D structure determination of proteins the backbone chemical shift assignment is the basis for a number of applications, like chemical shift perturbation mapping and studies on the dynamics of proteins. This assignment is not a trivial task even if a 3D protein structure is known and needs almost as much effort as the assignment for structure prediction if performed manually. We present here a new algorithm based solely on 4D [H-1, N-15]-HSQC-NOESY-[H-1, N-15]-HSQC spectra which is able to assign a large percentage of chemical shifts (73-82 %) unambiguously, demonstrated with proteins up to a size of 250 residues. For the remaining residues, a small number of possible assignments is filtered out. This is done by comparing distances in the 3D structure to restraints obtained from the peak volumes in the 4D spectrum. Using dead-end elimination, assignments are removed in which at least one of the restraints is violated. Including additional information from chemical shift predictions, a complete unambiguous assignment was obtained for Ubiquitin and 95 % of the residues were correctly assigned in the 251 residue-long N-terminal domain of enzyme I. The program including source code is available at https://github.com/thomasexner/4Dassign.
KW  - Chemical shift assignment
KW  - Protein
KW  - 3D structure
KW  - 4D NOESY
Y1  - 2016
U6  - https://doi.org/10.1007/s10858-016-0050-0
SN  - 0925-2738
SN  - 1573-5001
VL  - 65
SP  - 217
EP  - 236
PB  - Springer
CY  - Dordrecht
ER  - 
TY  - JOUR
A1  - Victora, Andrea
A1  - Moeller, Heiko M.
A1  - Exner, Thomas E.
T1  - Accurate ab initio prediction of NMR chemical shifts of nucleic acids and nucleic acids/protein complexes
JF  - Nucleic acids research
N2  - NMR chemical shift predictions based on empirical methods are nowadays indispensable tools during resonance assignment and 3D structure calculation of proteins. However, owing to the very limited statistical data basis, such methods are still in their infancy in the field of nucleic acids, especially when non-canonical structures and nucleic acid complexes are considered. Here, we present an ab initio approach for predicting proton chemical shifts of arbitrary nucleic acid structures based on state-of-the-art fragment-based quantum chemical calculations. We tested our prediction method on a diverse set of nucleic acid structures including double-stranded DNA, hairpins, DNA/protein complexes and chemically-modified DNA. Overall, our quantum chemical calculations yield highly/very accurate predictions with mean absolute deviations of 0.3-0.6 ppm and correlation coefficients (r(2)) usually above 0.9. This will allow for identifying misassignments and validating 3D structures. Furthermore, our calculations reveal that chemical shifts of protons involved in hydrogen bonding are predicted significantly less accurately. This is in part caused by insufficient inclusion of solvation effects. However, it also points toward shortcomings of current force fields used for structure determination of nucleic acids. Our quantum chemical calculations could therefore provide input for force field optimization.
Y1  - 2014
U6  - https://doi.org/10.1093/nar/gku1006
SN  - 0305-1048
SN  - 1362-4962
VL  - 42
IS  - 22
PB  - Oxford Univ. Press
CY  - Oxford
ER  -