NMR structure calculation for all small molecule ligands and non-standard residues from the PDB Chemical Component Dictionary
- 699 Downloads
An algorithm, CYLIB, is presented for converting molecular topology descriptions from the PDB Chemical Component Dictionary into CYANA residue library entries. The CYANA structure calculation algorithm uses torsion angle molecular dynamics for the efficient computation of three-dimensional structures from NMR-derived restraints. For this, the molecules have to be represented in torsion angle space with rotations around covalent single bonds as the only degrees of freedom. The molecule must be given a tree structure of torsion angles connecting rigid units composed of one or several atoms with fixed relative positions. Setting up CYANA residue library entries therefore involves, besides straightforward format conversion, the non-trivial step of defining a suitable tree structure of torsion angles, and to re-order the atoms in a way that is compatible with this tree structure. This can be done manually for small numbers of ligands but the process is time-consuming and error-prone. An automated method is necessary in order to handle the large number of different potential ligand molecules to be studied in drug design projects. Here, we present an algorithm for this purpose, and show that CYANA structure calculations can be performed with almost all small molecule ligands and non-standard amino acid residues in the PDB Chemical Component Dictionary.
KeywordsDrug design Protein–ligand complex Non-standard amino acid Molecular topology Structure calculation CYANA
We gratefully acknowledge financial support by the Lichtenberg program of the Volkswagen Foundation and a Grant-in-Aid for Scientific Research of the Japan Society for the Promotion of Science (JSPS).
- Allen FH, Bellard S, Brice MD, Cartwright BA, Doubleday A, Higgs H, Hummelink T, Hummelink-Peters BG, Kennard O, Motherwell WDS, Rodgers JR, Watson DG (1979) The Cambridge crystallographic data centre: computer-based search, retrieval, analysis and display of information. Acta Crystallogr Sect B Struct Commun 35:2331–2339Google Scholar
- Bahrami A, Assadi AH, Markley JL, Eghbalnia HR (2009) Probabilistic interaction network of evidence algorithm and its application to complete labeling of peak lists from protein NMR spectroscopy. PLoS Comp Biol 5:e1000307Google Scholar
- Klukowski P, Walczak MJ, Gonczarek A, Boudet J, Wider G (2015) Computer vision—based automated peak picking applied to protein NMR spectra. Bioinformatics. doi: 10.1093/bioinformatics/btv318
- Wüthrich K (1986) NMR of proteins and nucleic acids. Wiley, New YorkGoogle Scholar