This has been a great year for the Script Center. User feedback has been positive and we continue to provide a rapid turnaround for requests. We have added a considerable number of new scripts covering diverse topics ranging from quantum mechanics and molecular dynamics to cheminformatics and work workflow automation. We have also deployed workflows based on our recent publications. Below is a brief overview of some of the most popular scripts from 2009.
Score Phase Hypothesis by Glide XP Descriptors (i.e. E-Pharmacophores): This graphical interface automates the E-pharmacophore workflow from Salam et al. (J. Chem. Info. Model., 2009, 49(10) "Novel Method for Generating Structure-Based Pharmacophores Using Energetic Analysis"). A Phase pharmacophore hypothesis is generated based on the Glide XP descriptor energies associated with each pharmacophore feature. Optionally, fragment poses can be clustered by volume overlap to obtain spatially diverse poses that are then used to generate a de novo hypothesis, as was done in the work by Loving et al. (J. Comp. Aid. Mol. Des., 2009, 23 (8), "Energetic analysis of fragment docking and application to structure-based pharmacophore hypothesis generation").
R-Group Analysis: This was a recent addition to the Script Center at the end of 2009. A set of molecules is loaded into the graphical interface and the core is determined either from CombiGlide results, a user-submitted SMARTS pattern, or a Canvas Maximum Common Substructure. The core and fragments at each position can be visualized in a 2D heat map with coloring based on activity values or any other properties.
Pose Filter: While this script was around before 2009, it remains very popular. Glide docking results can be filtered based on user-defined receptor contacts/interactions. The user can choose which combination of ligand interactions should be used to define a contact (for example distance, H-bond, whether the contact is in a ring or aromatic ring). Multiple criteria can be given and the user can choose whether all or any of the interaction patterns must be matched.
Component Interactions: This simple graphical interface allows for the calculation of interaction energies between components of the receptor and one or more ligands. An automatic setup options allow for the calculation of either interactions between receptor residues and the ligand or ligand functional groups and the receptor.
Interaction fingerprints: This graphical interface is used to calculate ligand-receptor interaction fingerprints, screen by similarity, and cluster the results. An interactive matrix shows the interaction bits for all ligands and the structures are shown in the Workspace. Also, clicking cells in the clustering matrix shows 2D structures for each pair of ligands and the associated poses in the Workspace.
BREED: This is a re-implementation of the BREED algorithm from Vertex (J. Med. Chem. 2004, 47 (11) "Novel Inhibitors through Hybridization of Known Ligands."). Molecules in the same frame of reference (i.e. from superimposed crystal structures or docked ligands) are analyzed for overlapping bonds and hybridized to make new molecules.
Automation of Cross-docking Calculations: This is another script that has been on the Script Center for years and is still very popular. It is a command line script that takes a set of complexes as input and performs docking of each ligand into each receptor structure. The RMSD of the top pose relative to the native ligand is provided in an output matrix. Additionally, the ligand van der Waals radii are progressively scaled down for each ligand until a pose is recovered for cases where the ligand does not fit with full van der Waals radii. This script is particularly useful for analyzing the best set of receptors to use in ensemble docking.