typing in YASARA
Compared to the very high resolution data found
for example in the CSD ('Cambridge Structural Database'), the accuracy
of small molecules in the PDB is usually much lower. Especially bond
lengths and bond angles are often far away from their true values.
Still, the PDB contains a large number of protein-ligand complexes from
which a lot of crucial data for drug design could be derived, if it was
possible to identify and correct the ligand structures.
YASARA features an advanced molecule typer that
converts a point cloud of ligand atoms extracted from e.g. a PDB file
(CONECT records can be used if present) to an accurate representation
of the molecule including bond orders and hydrogen atoms, optionally
optimized by semi-empirical quantum mechanics.
The stages of the 'AutoSMILES' algorithm can be
summarized as follows:
- Assignment of hybridization states and initial bond orders
using an algorithm developed in collaboration with the OpenBabel team.
- Typing of ring systems by an algorithm that combines graph
theory with chemical knowledge about valence ambiguities and preferred
- Assignment of fractional bond orders that provide a
better picture of underlying symmetries and facilitate the automatic
assignment of force field parameters for molecular dynamics
simulations. The following color mapping is used in the examples on the
- Introduction of pH
dependency of bond orders and protonation states using a library of
- Optional conversion to a Kekulé form that avoids fractional
- Optional semi-empirical optimization using the AM1 or PM3
QM methods (requires YASARA Dynamics+).
- Fully automatic force field
parameter assignment to run simulations at the touch of a button.
All the examples on the right side have been typed in the absence of
hydrogen atoms and disregarding bond length information.