In YASARA Model and above, a
sophisticated small molecule builder is available to construct your
molecules manually in just a few seconds. (Alternatively, automatic
building from SMILES strings is supported in all YASARA stages, and larger molecules can be built from their sequence).
Movie 1 on the top right
shows how building works in practice, drawing on the example of
tiotropium, an anti-asthmatic bronchodilator known as 'Spiriva', which
is also shown in the bottom right figure 2. Interactive building is an
iterative process, where you select hydrogen atoms that should be
replaced or bridged with functional groups. YASARA provides over 50
groups to choose from, each with up to four alternative attachment
points. As known from 2D molecule editors, you can simply 'write' new
atoms and adapt bonds by typing on the keyboard, e.g. click on a
hydrogen and type 'C' to turn it into a CH3 group, or 'O' to turn it
into an OH group (hydrogens are thus added automatically).
It is also worth mentioning
that YASARA can record user input as a macro, generating the following
code while building the tiotropium in movie 1 (comments have been added
# Start with a 7-ring BuildGroup Cycloheptyl # Add nitrogen bridge BridgeAtom 9,18,Nitrogen # Add two methyl groups to nitrogen bridge SwapAtom 18 19,Carbon,UpdateBonds=yes,UpdateHyd=yes # Add oxygen bridge BridgeAtom 11,14,Oxygen # Add ester SwapAtom 1,Ester,AttachPoint=2 # Add methyl group SwapAtom 1,Carbon,UpdateBonds=yes,UpdateHyd=yes # Add hydroxyl group SwapAtom 2,Oxygen,UpdateBonds=yes,UpdateHyd=yes # Add thiophene rings SwapAtom 4 5,Pyrryl,AttachPoint=2 SwapAtom 5 14,Sulfur,UpdateHyd=yes
The screenshot in the middle
is from the help movie "4.1 Building small molecules", which starts
with an easier example (4-Iododiazenyl- 8-methyl- pyromellitimide) and
then continues with tiotropium.
The molecule builder makes extensive use of YASARA's knowledge about
pH-dependent bond orders and
protonation states. Having built the molecule, you can proceed
to optimize its geometry, either semi-empirically using the built-in
MOPAC, or empirically with automatic force field parameter assignment
using YASARA AutoSMILES.
The video above explains how to
build small molecules in YASARA. The example molecule is tiotropium,
which is a bronchodilator that relaxes muscles in the airways and
increases air flow to the lungs. Many
guiding through the movie.
1: Screenshot from YASARA's help movie 4.1, showing how to build
4-Iododiazenyl- 8-methyl- pyromellitimide. Users of the free YASARA
View can download the movie from the
repository. Double bonds are
2: Another view of tiotropium/Spiriva
shown in movie 1 above. Double bonds are colored