Brood is an extremely fast application for bioisostere prediction. Brood searches databases known chemical fragments at a rate of over 100 per second to identify molecular fragments that are similar to a query fragment. Brood identifies bioisosteres by finding fragments with shape, chemistry and electrostatics that are similar to a 3D query fragment.

Comparison of an ester fragment and an oxazole fragment showing the electrostatic isopotential contour surfaces. The electrostatic tanimoto between the two fragments is 0.54. Select image to enlarge.

The primary features of Brood include:

• Identifies bioisosteres of a query fragment from among a database of molecular fragments
• Packaged with two databases that are ready to search
• Shape, chemical and electrostatic bioisostere similarity
• Allows 1D, 2D or 3D query input
• Automatic conformer and partial charging of the query fragment
• Builds whole-molecule analogs of the query molecule based on bioisostere replacement
• Generates 3D overlay of each putative bioisosteric pair
• Can search more than 250,000 fragments per hour
• Output is ready to be imported into a spreadsheet
• OEChemplete - all I/O and molecular information processing by OEChem
• Robust reading and specification-compliant writing of SDF, MOL, MOL2, PDB, MacroModel, XYZ, and OEBinary file formats
• Support for LINUX, IRIX, Windows, OS X, AIX, HP-UX, Solaris, Tru64UNIX
• Support for 64-bit processing on IRIX, Itanium®2 Linux, PowerPC Linux, AIX, HP-UX and Tru64UNIX

Bioisosteric replacement has been a common medicinal chemistry technique for decades. OpenEye's tool is designed to aide modelers and medicinal chemists in the selection of bioisosteres. Brood offers insight into a problem medicinal chemists face on a daily basis. Brood consistently identifies the novel bioisosteric fragments as well as the bioisosteres a chemist would readily identify.

Brood has two pre-generated multiconformer fragment databases that are ready for searching. These databases were generated by breaking over 4 million drug, bioactive and vendor molecules into fragments. Brood also offers users the ability to build and search their own fragment databases. This suite includes a tool to fragment a molecular database into unique fragment libraries. The fragments can be generated using Broods default fragmentation scheme or a user supplied fragmentation scheme.

OpenEye is well known for its cheminformatics, 3D structure generation, and shape & electrostatic similarity technology. Brood applies each of these mature technologies to bioisostere identification. Bioisostere identification is a significant new area for OpenEye which historically has focused more heavily on developing hit and lead identification software.

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