FRAGMENT REPLACEMENT & GENERATIVE DESIGN

BROOD

BROOD is a generative chemistry program designed to help explore chemical and property space around a hit or lead molecule. BROOD generates analogs of the lead by replacing selected fragments in the molecule with fragments that have similar shape and electrostatics, yet with selectively modified molecular properties.

BROOD fragment searching has multiple applications, including lead-hopping, side-chain enumeration, generative design, patent breaking, fragment merging, property manipulation, and patent protection by SAR expansion.

Using OpenEye’s BROOD software for scaffold hopping, we successfully discovered a new chemical series from our lead compound, with equipotency and improved stability. – Laurent D., Lundbeck

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.

Features

Replace single- or multiple-fragments simultaneously in a single molecule
Edit queries graphically, modifying the similarity force-field and adding or removing chemical constraints critical to the SAR under development
Graphical interface to facilitate physical property analysis and real-time property filtering of millions of potential molecules
Integrated estimation of synthetic accessibility
Construction and assessment of new molecule series in a protein active-site
Hierarchical organization of the hitlist of analog molecules along with a new graphical interface designed specifically to explore and edit the hitlists
Database of more than 4 million medicinally relevant fragments provided and utilities to aid users in augmenting this database with novel fragments from their corporate collections
Available as a standalone GUI (vBROOD) or directly within Orion for cloud-based access

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

Multi-Query Fragment Replacement

BROOD is available as a standalone application or on cloud in Orion Molecular Design Platform. Using the BROOD workflow in Orion, scientists can generate single-site analogs or replace multiple fragments simultaneously with this 3D generative de novo design tool. Intelligent scoring and ranking manage the combinatorics of multi-fragment replacement, making it possible to explore vast molecular spaces efficiently. With no limit on the number of queries per molecule, BROOD gives scientists a generative design tool built on OpenEye's proven 3D science.