Quantum chemistry methods for rational drug design
Ended Project Grant Awarded Last action
- Award ID
- R43GM148095
- Recipient
-
Q-Chem Inc. UEI MXPESVR9KFE7
- Awarding agency
-
National Institute of General Medical Sciences
National Institutes of Health, Department of Health and Human Services
- Obligated
- $247,909
Award facts
- Assistance listing
- 93.859 Biomedical Research and Research Training
- Completion date
- Place of performance
- California, USA
Award details come from USAspending.gov.
Description
- Abstract
- A scalable computational quantum mechanics method for non-covalent protein-ligand interactions will be developed based on "extended" symmetry-adapted perturbation theory (XSAPT), a cubic-scaling, fragment-based approach that is specifically designed for large supramolecular complexes, and which affords a demonstrated accuracy of ;$ 1 kcal/MO! With respect to the best-available AB initio benchmarks. In phase I of this work, we will enhance the efficiency of XSAPT via better parallelization that will enable routine application to protein-ligand models containing 300+ atoms, using only modest computational resources. A bootstrap procedure will be developed to assess the accuracy of the method and a data set will be generated that includes protein-ligand interaction energies and their components: electrostatics, steric repulsion, dispersion, polarization, and charge transfer. The data set will build upon standard ones derived from crystal structures but will also include nonequilibrium structures as well as small ligand fragments for which crystal structures and other experimental data are not available; the latter are representative of fragment-based drug discovery strategies. These are challenging cases for interaction energy computations that can only be addressed quantitatively by using the predictive power of quantum mechanics, not by empirical scoring functions or by fits to experimental data. In phase II, this data set will be used to train a machine learning (ML) model that is capable of ranking-ordering ligand binding energies in a reliable and quantitative way, something that existing scoring functions ( even those based on ML) cannot do. Additional phase II work will integrate the ML-XSAPT scoring function into virtual drug-discovery workflows (including flexible docking protocols), which will facilitate both lead generation and lead optimization in drug discovery, based on quantitative AB initio energetics.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Original award | $247,909 |
Quick answers
Who received award R43GM148095?
R43GM148095 was awarded to Q-Chem Inc. by National Institute of General Medical Sciences (National Institutes of Health) on May 15, 2023.
How much is award R43GM148095 worth?
$247,909 has been obligated on R43GM148095.
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