Dr. Sherman works closely with researchers using Schrödinger software for molecular modeling and drug design projects. In this newsletter, Dr. Sherman talks about cheminformatics tools and 2D representation within Maestro , the new Workspace Assistant, and more. All of the scripts discussed here can be downloaded from the Schrödinger Script Center.
Q: I have always wanted to display 2D images of my ligands within Maestro. Is there a way to do this?
A:
We are very happy to announce that Maestro can now create very nice 2D.
The 2D Viewer, located under the Scripts menu in Maestro, provides a
grid view that is interactive with the Project Table and Workspace.
There are options to include one or more properties in the cell with
the 2D image. In future versions we will allow for printing/saving the
table as a PDF or html document. For now, you can use generate_2d_report.py (available on the Script Center) to generate html and PDF reports. Once you have installed your scripts (ideally with the Update… button), just type:
$SCHRODINGER/run generate_2d_report.py
This is how all of the command line scripts can be run.
Q: I have a favorite way that I like to setup my Workspace. For example, I always want the ligand shown in ball & stick with green carbons, the protein in wire with elemental coloring, and ions shown in CPK. Is there an easy way to do this automatically without having to set these for each entry?
A:
Yes. Also located under the Scripts menu in Maestro you can find the
Workspace Assistant. This new interface provides a very nice way to set
your Workspace preferences, which will automatically get applied to
anything in the Workspace. In addition to having control over atom
color, molecular representation, and other style options; you can also
choose to show contacts, H-bonds, and surfaces. You can save your
favorite settings to be used in all your Maestro sessions. The
Workspace Assistant is active as long as the panel is open. To turn it
off, just close the panel.
Q: Can I perform 2D similarity searching or clustering within Maestro?
A: Yes, with our new Similarity and Clustering GUI, canvas_cluster.py,
it is easy to perform similarity searches and clustering in Maestro. We
provide access to 7 fingerprint types, 10 atom typing schemes, 22
similarity metrics, and 9 linkage methods, giving full user control
over similarity and clustering. Interactive plots make selecting the
optimal number of clusters easy and intuitive. The clustering distance
matrix can be visualized with interactive cells that link to 2D images
of the structures. If instead of similarity clustering you are
interested in generating a diverse subset, you can choose to only
return the structure closest to the midpoint of each cluster. This
script is located under the Cheminformatics section.
Q: The 2D clustering described above is nice, but for structure-based projects is there a way to cluster based on spatial occupancy (i.e. volume overlap)?
A: Volume Cluster (volume_cluster.py)
computes the volume overlap between atoms of different entries and then
performs hierarchical clustering to return a group of structures to the
Project Table for each cluster. This can be very useful for
applications such as fragment docking in which "hot spots" of the
binding site are of interest. It can also be used to cluster loop
conformations or structures that do not have consistent atom numbering,
which is needed to perform an RMSD-based clustering. This script is
also located under Cheminformatics.
Q: I have just completed my first Desmond molecular dynamics simulation and want to start analyzing the trajectories. The Simulation Quality Analysis interface is a nice way to see the statistics and plots associated with general simulation data (energy, pressure, volume, etc.) but now I want to compute more detailed terms and explore interesting events in the simulation. How can I do this?
A: We have a Simulation Event Analysis script that was just recently posted on the Script Center.
It can be used to compute many properties of your simulation, such as
RMSD to any frame, H-bonds to/within any molecule, energetic
breakdowns, and measurements between any atoms in the system (distance,
angle, torsion, or planar angle). Results can be plotted as a time
series or histogram. The time series plot is interactive, such that
clicking on any point will result in that structure being displayed in
the Workspace. This script is located under Molecular Dynamics.
Q: I have used the pose_filter.py script in the past and find it very useful for analyzing and post-processing my Glide docking results. Is there a way to use this script through a graphical interface?
A: Yes, we recently developed a Pose Filter GUI in pose_filter.py.
It allows for filtering based on one or more criteria, such as hydrogen
bonds to selected residues, aromatic contacts, or ring contacts. It is
available under Docking Post-processing.
Q: I have a bunch of crystal structures of the same target with different ligands. I would like to create new molecules that could be made based on how the existing molecules overlap. Basically, I want to apply the BREED technology developed by researchers at Vertex Pharmaceuticals?
A: We just implemented the BREED algorithm (A.C. Pierce, "Novel Inhibitors through Hybridization of Known Ligands," J. Med. Chem., 2004, 47, 2768-2775).
The algorithm looks for bonds between different molecules that align
reasonably well and then swaps the fragments of the two molecules on
either side of the bond. This "breeding" of molecules can be performed
over multiple generations to produce many molecules from a small
starting pool. In addition to running on superimposed crystal ligands,
it can also be run on Glide docking results to generate new ideas and molecules. This script, breed.py, is located under Fragments.
Q: I have some results from a fragment docking calculation and would like to explore ways to connect them. I have used fragment_join.py from the Script Center and that works well for cases in which the fragments are very close or could be connected by up to 2 methylene linkers, but in some cases the fragments have greater separation. What can I do?
A: We have a fragment linking script (fragment_link.py)
to do this. It takes in a set of docked fragments and a file of
potential joining cores and links the fragments with the cores. The
score is based on how well the bonds of the core align with the
fragment bonds. This script is located under Fragments.
Q: I have installed all of your scripts using the Update… option under the Scripts menu (wow, that was easy!), but I find that my colleagues cannot see the scripts installed in their Maestro sessions. How to I ensure that my colleagues have access to the scripts as well?
A: We have both a local user area and a common area for our Python scripts. By default, your scripts go into the user area, which will only be accessible by you. However, if someone with administrator privileges in your $SCHRODINGER directory does the update they can select the common area and the scripts will be available to all users. This is our recommended way of installing the scripts. Ask your administrator to update the scripts regularly to ensure you have all enhancements and new scripts.