# Structure Determination Technology (592-634)

> **NIH NIH P41** · NEW YORK STRUCTURAL BIOLOGY CENTER · 2020 · $49,306

## Abstract

Atomic structures of membrane proteins are playing a major role in understanding the mechanisms of action and
deriving fundamental principles for these systems. Crystallography is the dominant method for obtaining membrane
protein structures at atomic and near atomic resolutions, single-wavelength anomalous diffraction (SAD)
predominates for de novo structure determination, which is essential in many instancs. Recently x-ray free electron
lasers for crystallography and direct electron detectors for single-particle cryo electron microscopy (cryo-EM) emerging
as technologies for solving challenging structures of membrane proteins and their complexes. Nevertheless,
bottlenecks remain including weak anomalous signals, micron-sized crystals and radiation damage in crystallography
and atomic interpretation of electron density maps from cryo-EM. We propose to address these bottleneck challenges
in four sub-projects. Aim 1 (TR&D 4.1) focuses on the extraction of signals from weak anomalous scatterers with the
aim of making native-SAD analysis robust even for low-resolution membrane protein structures. Aim 2 (TR&D 4.2)
relates to challenges in the manipulation and analysis of microcrystals, including the development of new methods for
mounting microcrystals presentation in microdiffraction experiments and methods of analysis for optimal synthesis of
complete data sets from the partial data of many crystals. Aim 3 (TR&D 4.3) is concerned with the mitigation of
radiation damage, which is exacerbated in measurements from microcrystals as needed for optimal native-SAD
analyses. Aim 4 (TR&D 4.4) will address the optimized fitting of atomic models to cryo-EM maps. We will innovate
methods for identifying specific residues types in such maps and methods for a sorted classification of ligand-binding
populations for optimized placement of the ligands and associated conformational changes.

## Key facts

- **NIH application ID:** 9939557
- **Project number:** 5P41GM116799-05
- **Recipient organization:** NEW YORK STRUCTURAL BIOLOGY CENTER
- **Principal Investigator:** WAYNE A. HENDRICKSON
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $49,306
- **Award type:** 5
- **Project period:** — → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939557

## Citation

> US National Institutes of Health, RePORTER application 9939557, Structure Determination Technology (592-634) (5P41GM116799-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9939557. Licensed CC0.

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