title: NMR structure calculation for all small molecule ligands and non-standard residues from the PDB Chemical Component Dictionary.
abstract: 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.
authors.affiliation: Center for Biomolecular Magnetic Resonance, Institute of Biophysical Chemistry, Goethe University Frankfurt am Main, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany.
authors.forename: Emel Maden
authors.initials: EM
authors.lastname: Yilmaz
authors.affiliation: Center for Biomolecular Magnetic Resonance, Institute of Biophysical Chemistry, Goethe University Frankfurt am Main, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany. guentert@em.uni-frankfurt.de.|Laboratory of Physical Chemistry, ETH Zürich, Zurich, Switzerland. guentert@em.uni-frankfurt.de.|Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo, Japan. guentert@em.uni-frankfurt.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Güntert
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors; D000072198:ADAM17 Protein; D000596:Amino Acids / Q000737:chemistry*; D062126:Databases, Chemical; D030562:Databases, Protein; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008024:Ligands; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000494:pharmacology; D054852:Small Molecule Libraries / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D004791:Enzyme Inhibitors; D008024:Ligands; D009842:Oligopeptides; D054852:Small Molecule Libraries; C078372:JMV 390-1; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C456839:pyrrolysine; D008239:Lysine
keywords: CYANA; Drug design; Molecular topology; Non-standard amino acid; Protein–ligand complex; Structure calculation