e Total Flare Designer 5-user group license 1-year term March 30, 2021 to March 29,2022

he National Institutes of Health (NIH) is the nation’s leading medical research agency and the primary Federal agency whose mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability, conducting, supporting and making medical discoveries that improve people’s health and save lives. The National Center for Advancing Translational Sciences (NCATS) is a part of the National Institutes of Health (NIH), which mission it is to catalyze the generation of innovative methods and technologies that will enhance the development, testing and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions. The Early Translational Branch (ETB) is tasked with identifying and developing novel small molecule leads against a wide spectrum of human disease targets, which it accomplishes by screening thousands of small molecules in collaboration with both intra-and extramural researchers. In pursuit of this goal, the Center has a strong internal trans-disciplinary team of scientists who continually discover novel small molecules for application against a wide range of human diseases. As such, discovering probe molecules that could serve as starting points for therapeutics is of great interest within NCATS. NCATS use several strategies and tools to address many aspects of design approaches to discover novel, effective small molecules. Cresset's Flare software platform will help to design using advanced approaches for protein-ligand analysis for the structure-based design of ligands. Computational, medicinal and synthetic chemists at NCATS will use this software on a daily basis as a part of their work flow. NCATS is in need of software that can perform the following: • The software shall be based on field technology, a feature that uses biological activity rather than chemical similarities as the key descriptors of the molecule •The software shall be get accurate values for relative binding affinity within a related set of ligands using Free Energy Perturbation (FEP) • The software able to study the conformational changes of proteins and assess the stability of protein-ligand complexes using Molecular Dynamics experiments • The software shall use choice of force fields for FEP and Dynamics calculations, including Open force field • The software shall get immediate feedback on where ligands complement proteins and use this in design • The software shall assist to design new molecules and dock them to protein target • The software shall be able minimize protein-ligand complexes to achieve optimal interaction for each compound • The software shall use the energetics of ligand binding to guide lead optimization • The software shall be able to calculate the location and stability of water molecules in your protein • The software shall be able Automate and customize workflows and add new menu entries through the Python API • The software shall be able to integrate into already subscribed FORGE and SPARK tools