An Integrated Approach to Library Design

presentation · 12 years ago
by Patrick Walters (Vertex Pharmaceuticals)
A chemist designing a combinatorial library must consider many criteria when selecting reagents for synthesis. Factors such as target potency, physical properties, metabolic stability, and off-target activity are among many parameters that must be optimized. Although computational models exist to aid the chemist, these models are often poorly validated and are not easily integrated into the drug discovery process. As part of a continuing effort to provide library design tools for medicinal chemists, we have created a software tool known as Reaction Planner. This software provides an easy means of linking a virtual combinatorial library with a well-validated set of computational models. The application of these models can dramatically reduce the size of a virtual library, and help to focus a chemistry effort on the most relevant compounds. Models in Reaction Planner are constructed using NOMAD, an internally developed software platform that allows computational chemists to identify optimal combinations of molecular descriptors and machine learning methods. Models generated using NOMAD can then be published to Reaction Planner where they become part of the medicinal chemistry workflow. This presentation will provide an overview of NOMAD and Reaction Planner, as well as example applications