SHIFTS takes a protein structure in Brookhaven (PDB) format, and computes
proton chemical shifts from empirical formulas. It can also compute
N, Cα, Cβ and C' shifts in proteins, using a database based
on DFT calculations on peptides. It also provides an "afnmr" (Automated
Fragemention approach for NMR) to compute chemical shifts and anisotropies in
Starting in Oct. 2018, we are also packaging up the afnmr functionality
in a separate package, which is self-contained and does not require
AmberTools. See below for more information. (Note: this package contains the
most up-to-date vesion of the afnmr functionality, and is the one that
will be maintained going forward.)
The basic ideas are presented in the
- K. Osapay and D.A. Case. A new analysis of proton chemical
shifts in proteins. J. Am. Chem. Soc.
113, 9436-9444 (1991).
- K. Osapay and D.A. Case. Analysis of proton chemical shifts in
regular secondary structure of proteins. J. Biomol. NMR
4, 215-230 (1994).
- D.F. Sitkoff and D.A. Case. Density functional calculations of proton
shifts in model peptide systems. J. Am. Chem. Soc. 119,
- D. Sitkoff and D.A. Case. Theories of chemical shift anisotropies in
proteins and nucleic acids. Prog. NMR Spectr. 32, 165-190 (1998).
- A. Dejaegere and D.A. Case. Density functional study of ribose and
deoxyribose chemical shifts. J. Phys. Chem. 102, 5280-5289 (1998).
- A.P. Dejaegere, R.A. Bryce and D.A. Case. An empirical analysis of
shifts in nucleic acids. In Modeling NMR Chemical Shifts, J.C.
Facelli and A.C. de Dios, eds. (Washington, American Chemical Society, 1999),
- X.P Xu and D.A. Case. Automated prediction of 15N,
13Cα, 13Cβ and 13C' chemical shifts in proteins
using a density functional database. J. Biomol. NMR. 21, 321-333
- X.P. Xu and D.A. Case. Probing multiple effects on 15N,
13Cα, 13Cβ and 13C' chemical shifts in peptides
using density functional theory. Biopolymers 65, 408-423 (2002).
- S. Moon and D.A. Case. A new model for chemical shifts of amide hydrogens
in proteins. J. Biomol. NMR 38, 139-150 (2007).
- X. He, B. Wang, and K.M. Merz, Jr. Protein NMR Chemical Shift Calculations
Based on the Automated Fragmentation QM/MM Approach. J. Phys. Chem. B
113, 10380-10388 (2009).
- T. Zhu, X. He, and J.Z.H. Zhang. Fragment density functional theory
calculation of NMR chemical shifts for proteins with implicit solvation. Phys.
Chem. Chem. Phys. 14, 7837-7845 (2012)
- T. Zhu, J.Z.H. Zhang, and X. He. Automated Fragmentation QM/MM Calculation
of Amide Proton Chemical Shifts in Proteins with Explicit Solvent Model. J.
Chem. Theory Comput. 9, 2104-2114 (2013)
- S. Tang and D.A. Case. Calculation of chemical shift anisotropy in
proteins. J. Biomol. NMR 51, 303-312 (2011).
- D.A. Case. Chemical shifts in biomolecules. Curr. Opin. Struct. Biol.
23, 172-176 (2013).
- J. Swails, T. Zhu, X. He and David A. Case. AFNMR: Automated fragmentation
quantum mechanical calculation of NMR chemical shifts for biomolecules.
J. Biomol. NMR 63, 125-139 (2015).
Here are some recent applications:
- H. Zhang, G. Hou, M. Lu, J. Ahn, I.-J. Byeon, C.J. Langmead, J.R.
Perilla, I. Hung, P.L. Gor'kov, Z. Gan, W. Brey, D.A. Case, K. Schulten, A.M.
Gronenborn, and T. Polenova. HIV-1 Capsid Function is Regulated by Dynamics:
Quantitative Atomic-Resolution Insights by Integrating Magic-Angle-Spinning
NMR, QM/MM, and MD. J. Am. Chem. Soc. 138, 14066-14075 (2016).
- M. Fritz, C.M. Quinn, M. Wang, G. Hou, X. Lu, L.M.I. Koharudin, J.
Struppe, D.A. Case, T. Polenova and A.M. Gronenborn. Accurate determination of
backbone chemical shift tensors in microcrystalline proteins by integrated MAS
NMR and QM/MM. Phys. Chem. Chem. Phys. 20, 9543-9553 (2018).
- H. Shi, M.C. Clay, A. Rangadurai, B. Sathyamoorthy, D.A. Case, and
H.M. Al-Hashimi. Atomic Structures of Excited State A-T Hoogsteen Base Pairs
in Duplex DNA by Combining NMR Relaxation Dispersion, Mutagenesis, and
Chemical Shift Calculations. J. Biomol. NMR 70, 229-244 (2018).
The latest version (5.5, June, 2018) can be obtained from:
Some version history:
- Version 4.1.2 is a minor bug-fix release compared to versions 4.1 and 4.1.1,
required primarily for some Linux machines and for compatibility with the
latest version of NAB. If you have version 4.1 or 4.1.1, and it passes the
test suite, you should not need to download the updated version.
- Version 4.2 adds a new model for estimating amide proton shifts in proteins.
It is described in paper 9, above.
- Version 4.3 just has a minor fix to the
lsq program, and updates the
- Version 5.0 is a major rewrite; it updates the empirical formulaas for
proton shifts in nucleic acids, and adds the afnmr capability, described in
papers 10-15 above. Version 5.0.1 contains minor tweaks and adds a
protein-DNA complex example.
- Version 5.1 is an update to coincide with AmberTools16.
- Version 5.2 fixes a bug in fragmentation that could sometimes leave out
carbonyl acceptors in proteins; adds better support for water and ligands, and
for choosing which residues to analyze.
- Version 5.3 slightly modifies the minimization procedure; uses residue
numbers from the input pdb file (rather than a sequential number starting at
- Version 5.4 mainly changes the default basis sets (to the pcSseg-n group
from Frank Jensen), and adds other, mostly minor, convenience features.
- Version 5.5 includes some code cleanup, and support for deMon version 5.
You will need the AmberTools package (see
in order to compile SHIFTS.
Both AmberTools and SHIFTS are distributed under the GNU General Public License (GPL).
The latest version (1.1, July, 2019) of the afnmr package
can be obtained from:
Installation and usage instructions are in the afnmr.pdf file, in the
"doc" folder. As noted above, afnmr is fully self-contained, and
does not require AmberTools.
Version 1.1 is a minor update from version 1.0, mainly making it easier
to use snapshots for solvated molecular dynamics simulations as inputs.
Updated on July 5, 2019. Comments to email@example.com