# High-resolution molecular recognition of ligands using solution X-ray scattering

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2022 · $319,000

## Abstract

PROJECT SUMMARY
 Protein-ligand interactions are fundamental to virtually all biological organisms and thus are the primary focus
of pharmaceutical therapies. Yet these interactions are difficult to study due to current limitations in available
structural methods. 3D atomic structures of protein-ligand complexes have dramatically increased our
understanding of molecular recognition, resulting in the development of structure-based drug design and its
fundamental integration into medicinal chemistry. X-ray crystallography is the primary tool for structure
determination of macromolecules and is capable of elucidating high-resolution atomic interactions between
proteins and ligands, yet suffers from experimental limitations such as the bottleneck of crystallization and the
inability to reveal dynamic structural states. Solution scattering provides a mechanism for modeling the structure
and dynamics of molecules in solution, yet current methods only provide low-resolution information, insufficient
for characterizing atomic level interactions between ligands and proteins.
 Here we propose a collection of new algorithms combining solution scattering with structural information
obtained by methods such as crystallography for the determination of high-resolution structure and dynamics of
protein-ligand complexes in solution. The successful completion of the aims of this proposal will enable
researchers to identify the atomic-level interactions resulting in molecular recognition of ligands such as drugs
and other small molecules. As solution scattering experiments can be performed in high-throughput, these
developments promise to increase the rate at which pharmaceuticals can be screened and characterized. These
insights will ultimately play an important role in developing novel therapeutics and improving approaches to
structure-based drug design, allowing for more specific and effective treatments of a wide range of diseases.

## Key facts

- **NIH application ID:** 10455698
- **Project number:** 5R01GM133998-04
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Thomas D. Grant
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $319,000
- **Award type:** 5
- **Project period:** 2019-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455698

## Citation

> US National Institutes of Health, RePORTER application 10455698, High-resolution molecular recognition of ligands using solution X-ray scattering (5R01GM133998-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10455698. Licensed CC0.

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