Accelrys Software: CATALYST

Catalyst provides an integrated environment for database management and querying tasks that are extremely valuable in drug discovery research.

This integrated environment allows for seamless access to complementary capabilities such as pharmacophore-based alignment of molecules, shape-based three-dimensional searching, automated generation of pharmacophore hypotheses based on SAR data, and generation of multiple conformations with extensive coverage of conformational space.

Catalyst operates on IBM® eServer[TM] systems running IBM AIX®, Intel-based Linux PC's and Silicon Graphics® UNIX workstations and servers.

Catalyst/COMPARE provides the ability to compare and fit hypotheses onto molecules.

Catalyst/VISUALIZER provides an easy-to-use modeling, 3D query editing, and structural editing and search environment for collaborative studies by molecular modeling experts and practising chemists.

Catalyst/SHAPE takes a specified 3D conformation and identifies compounds that possess similar 3D shapes. Catalyst/SHAPE complements the powerful pharmacophore and hypothesis-based searching also available within Catalyst.

ConFirm generates coverage-based conformational models for exploring energetically accessible flexibility in large libraries of compounds.

Catalyst Analysis and Management

Catalyst/INFO builds and administers databases of 3D structures from your own corporate or project data.

Catalyst Databases provide hundreds of thousands of potential lead compounds, accessed through Catalyst's advanced information retrieval, analysis, and simulation capabilities. Databases include Chemicals Available for Purchase(CAP), and BioByte Master File. In addition, DBServer comes pre-loaded with NCI databases and the Maybridge catalog.

Catalyst Jubilant Kinase Database provides the industry's largest collection of kinase inhibitors with about 165,000 compounds. Over 60,000 compounds contain biological activity data (IC50, Ki, etc), mechanism of action, assay information, target structure information, patent information, etc.

Catalyst DBServer identifies leads by using a hypothesis/pharmacophore that may include binding features, structural and property constraints, as a search query against databases containing hundreds of thousands of molecules. DBServer considers fully 3D flexibility, while at the same time delivering unparalleled performance. DBServer comes preloaded with the Maybridge catalog and NCI databases.

CatDBLibrary provides a novel means of building Catalyst-formatted databases of large virtual and real combinatorial libraries from Markush templates. This module is essential for generating good quality, diverse conformer models that contain repeated R-groups. CatDBLibrary's underlying algorithm exploits the combinatorial nature of the library under construction to accelerate conformational model generation. Alternatively, you have an option to use pre-computed conformational models when generating libraries. CatDBLibrary also utilizes distributed computing resources for speed and flexibility.

Pharmacophore Identification using Catalyst

HypoGen generates 3D hypotheses to explain variations of activity with the structure of drug candidates. This helps you to concentrate experiment on likely active compounds. HypoGen operates on a range of activity data.

HipHop performs feature-based alignment of a collection of compounds and generates pharmacophore models. HipHop is used to match features, such as surface-accessible hydrophobes, surface-accessible hydrogen bond donors/acceptors, and charged/ionizable groups, against candidate molecules or searches of 3D databases.

HypoRefine performs the automated generation of exclusion volumes in simulated annealing optimization of pharmacophore models in activity-based hypothesis generation. This module will add one or more excluded volumes to HypoGen models, to improve regression coefficients, and accuracy of activity predictions. For systems where steric effect plays a role in modulating biological activity, HypoRefine provides more realistic pharmacophore-based SAR model detecting activity trends between several ligands and a biological target.