Bioisostere TK

Bioisostere TK generates analogs by fragment replacement, replacing a portion of a lead compound with fragments that have similar 3D properties but potentially novel connectivity and chemistry. To ensure synthetic accessibility of its results Bioisostere TK ships with a database of fragments derived from ChEMBL, while custom databases of fragments can be created from any set of molecules using both pre-defined and tailored rules.

The toolkit provides fragment-based modeling tools, including fragment creation, fragment conformer generation, and fragment alignment and scoring using similarity based on physically meaningful representations: shape, chemical features, and electrostatics.

Bioisostere TK provides programmatic access to the existing BROOD and CHOMP applications.

Bioisostere TK fragment overlay between a reference and a fit fragment, based on shape and color. The attachment points in both the reference and fit fragments are marked in purple. The fragment overlay highlights how special attention is paid to the overlay of the attachment points.

De novo design using an EZH2 inhibitor. The input molecule (left) is divided into three fragments to build three separate BROOD queries. The molecule on the right was designed with Bioisostere TK by replacing all three queries at once.

Multi-Query Fragment Replacement

Bioisostere TK enables both single-site and multi-site fragment replacement. The combinatorics of multi-fragment replacement are handled by intelligent scoring and ranking, exploring potentially gigantic molecular spaces efficiently. With no limit on the number of fragments per molecule, Bioisostere TK is a scalable foundation for building generative design applications on the proven science in our 3D similarity tools.

Modeling

The Modeling suite of toolkits provides the core functionality underlying OpenEye's defining principle that shape & electrostatics are the two fundamental descriptors determining intermolecular interactions. Many of the toolkits in the Modeling suite are directly associated with specific OpenEye applications and can, therefore, be used to create new or extend existing functionality associated with those applications.

OEChem TK OEChem TK Core chemistry, advanced peptide handling, and high-performance molecule file I/O
FastROCS™ TK Real-time shape similarity for virtual screening, lead hopping & shape clustering
OEDocking TK Molecular docking and scoring
Omega TK Conformer generation
Shape TK 3D shape description, optimization, and overlap
SiteHopper TK Rapid comparison of protein binding sites
Spicoli TK Surface generation, manipulation, and interrogation
Spruce TK Protein preparation and modeling
Szybki TK Force field based focused optimization and entropy estimations
OEFF TK Force fields and general optimization tools
Szmap TK Understanding water interactions in a binding site
Zap TK Calculate Poisson-Boltzmann electrostatic potentials
Bioisostere TK 3D fragment similarity, lead optimization, and analog generation
Eon TK Molecular shape and electrostatic overlap

Cheminformatics

The Cheminformatics suite of toolkits provides the core foundation upon which all the OpenEye applications and remaining toolkits are built.

OEChem TK OEChem TK Core chemistry, advanced peptide handling, and high-performance molecule file I/O
OEDepict TK 2D Molecule rendering and depiction
Grapheme™ TK Advanced molecule rendering and report generation
GraphSim TK 2D molecular similarity (e.g. fingerprints)
Lexichem™ TK Name-to-structure, structure-to-name, foreign language translation
MolProp TK Molecular property calculation and filtering
Quacpac TK Tautomer enumeration and charge assignment
OEMedChem TK Matched molecular pair analysis, fragmentation utilities, and molecular complexity metrics
Saiph TK: Extracting, transforming, and loading (ETL) files and records