FAQs

CORINA Classic is a rule- and data-based 3D molecular model builder. The system can be regarded as a fully automatic 3D model building kit. By combining mono-centric fragments with standard bond lengths and angles and by using appropriate dihedral angles a 3D model of a molecule is built. Bond lengths and angles possess only one rigid minimum and are taken from tables. Since multiple solutions exist for torsion angles, two major problems arise. First, in ring systems only restricted sets of torsion angles are allowed that ensure proper ring closure. Secondly, non-bonded interactions due to flexible chain portions have to be minimized. Therefore, CORINA Classic handles ring and chain portion in a molecule separately.

Rings of up to a size of nine atoms are processed by using a table of allowed, single ring conformations that implicitly ensure ring closure. In the case of fused or bridged systems, a backtracking search procedure finds a contradiction-free set of conformations for each single ring following some geometric and energy restrictions.

The generated ring conformations are further refined applying a simplified “pseudo” force field that contains only special geometric terms to relax the ring geometries and to identify a low-energy conformation.

For acyclic fragments and molecules, the principle of longest pathways has been implemented. The main chains are extended as much as possible by setting the torsion angles to anti or trans configurations, unless a cis double bond is specified. This method effectively minimizes non-bonding interactions, such as atom overlaps or close contacts.

After the combination of the three-dimensional fragments of the ring systems and of the acyclic parts, the entire 3D model is checked for overlapping atoms and for close contacts. If such situations are detected, CORINA Classic performs a reduced conformational analysis in order to avoid these interactions. It varies the torsion angles of strategic bonds in the molecule applying values from small molecule crystal structures until the non-bonded interactions are solved.

Finally, the 3D molecular model is output in the required file format.

An input file that contains SMILES or InChI alongside with other compound information (such as names, IDs, properties) may provide the name of the compound in a particular column. How can CORINA Classic be told from which column it should read the compound name and parse it to the respective name field in the output file?

The input option “-i nc#=N” can be used, where N is the number of the column in which the name of the SMILES or the InChI is stored. The name is then copied to the name field of the respective output format (e.g., a SYBYL MOL2 output file). The abbreviation “nc#” stands for “name column number”.

An input file that contains SMILES or InChI alongside with other compound information (such as names, IDs, properties) may not provide the structure information (SMILES, InChI) in the first column. How can CORINA Classic be told from which column it should read the structure information?

By default, CORINA Classic expects the structure information (as a SMILES string or InChI) in the first column of the input file. The input option “-i sc#=N” can be used, if the structure information is provided in any other column than the first one. The number “N” is the number of the column in which the SMILES or the InChI is stored. The abbreviation “sc#” stands for “structure column number”.

CORINA Classic is parametrized for the entire periodic table (up to 103 Lawrencium) and all molecules that can be expressed in a valid valence bond (VB theory) notation can be processed.

CORINA Classic does not calculate “real” energies such as obtained from force field or quantum mechanical calculations. Internally, CORINA Classic uses symbolic energy values (that have been derived from FF calculations) and terms for ring systems and non-bonded interactions.

For ring systems, a full conformational analysis is performed in order to identify a low-energy conformation.

Finally, the ring systems are relaxed in a so-called “pseudo” force field to optimize the ring skeletons, but without calculating any “real” energy values.

CORINA Classic cannot generate 3D structures for pi complexes. It processes only molecules that can be expressed in a vald valence bond (VB theory) notation and with atoms with up to a maximum of six bonded neighbors (coordination number of 6).

In general, CORINA Classic does not have any limitations regarding the number of atoms or bonds of an input structure that should be converted into 3D. However, CORINA Classic has been designed to process small to medium sized organic, drug-like molecules. The larger a molecule gets the more the intra-molecular interactions gain in importance influencing the secondary structure of a molecule. CORINA Classic can model these interactions only to a limited extend and, therefore, is not able to correctly predict 3D structures of polymers and biopolymers such as proteins, enzymes or nucleic acids.

Basically, there are no limitations regarding the number of atoms or the number of ring atoms in a molecule. However, some file formats do not support more than 999 atoms (or bonds), such as the SD file (V2000).

There is also no limitation regarding the number of records (i.e., molecules) in an input file. CORINA Classic consecutively processes all records in the file and writes out the generated 3D models. Please note that hardware platforms and operating systems might have some limitations regarding the file size.

CORINA Classic does not need the 2D information (or structure depict) of a molecule but the connection table (CT) information of a molecule. This information is provided in standard file formats for chemical information (such as SD file or SMILES). CORINA Classic can also generate a 3D structure from an input SD file if all coordinates are set to zero (SMILES also does not provide 2D information).

Since the first commercial version of CORINA Classic, it is fully aware of stereochemistry.

CORINA Classic interprets stereo descriptors in SMILES (“@” and “@@” for tetrahedral centers; “//” and “/\” for double bonds) and SD files (wedge symbols in the bond block; parity flags in the atom block). Furthermore, CORINA Classic is able to interpret input 3D structures and to determine the correct stereo chemistry from read-in 3D information (e.g., in SYBYL MOL2 files).

There is one exception when 2D (or 3D) coordinates are required, i.e., for E/Z specifications of double bonds in SD files. If no coordinates are provided in an SD input file, CORINA Classic cannot derive the configuration of a double bond, as there are no separate descriptors (such as wedged bonds or parity flags for tetrahedral chiral centers) available for double bonds. This is true for both SD V2000 and v3000 formats.

The best way to cite CORINA Classic is to use the following three references.

(a) Sadowski, J.; Gasteiger, J.; Klebe, G. Comparison of Automatic Three-Dimensional Model Builders Using 639 X-Ray Structures. J. Chem. Inf. Comput. Sci. 1994, 34, 1000-1008 (DOI: 10.1021/ci00020a039z

(b) Schwab, C.H. Conformations and 3D pharmacophore searching. Drug Discovery Today: Technologies, Volume 7, Issue 4, Winter 2010, e245-e253 (DOI: 10.1016/j.ddtec.2010.10.003)

(c) 3D Structure Generator CORINA Classic, MN-AM, Molecular Networks Altamira, Nuremberg, Germany, www.mn-am.com