# Structural Dynamics at LCLS

> **NIH NIH P41** · STANFORD UNIVERSITY · 2021 · $1,594,586

## Abstract

ABSTRACT: OVERALL
The goal of this proposal is to form a Biomedical Technology Research Resource (BTRR) at SLAC National
Accelerator Laboratory that involves a set of interrelated Technology Research and Development (TR&D)
projects aimed at enhancing and developing the unique capabilities of the SLAC Linac Coherent Light Source
(LCLS) for biomedical applications. The BTRR will enable structural biology experiments that are extremely
difficult or impossible to perform at synchrotron (SR) or electron microscopy (cryoEM) facilities and will increase
the availability of these capabilities to the broader structural biology community. The enabled experiments will
facilitate paradigm-shifting advances on a wide variety of topics, including neurotransmission, signal
transduction, cellular metabolism, transcription and viral infection. The proposed TR&Ds are tightly coupled with
the research themes of the nine Driving Biomedical Projects (DBPs). These research themes focus on
developments to visualize large complexes and membrane proteins, such as GPCRs and that provide accurate
active site structures of metalloenzymes, such as ribonucleotide reductase and cytochrome c oxidase, and
complex macromolecular machines, such as RNA polymerase-II. Finally, a common research area of all DBPs
involve time-resolved (TR) studies that include research to follow dynamic processes involved in adenine
riboswitch signaling, the transport mechanism of N. gonorrhoeae MtrF, antibiotic binding to β-lactamase and
examination of interaction specificity of CypA variants.
All DBPs hinge on highly efficient data collection methods, which are required for successful macromolecular
crystallography (MC) experiments at X-ray FELs. The high peak brightness of an X-ray FEL pulse destroys the
crystal volume exposed, bringing about sample refreshment challenges previously unknown to the MC SR
community. As a result, the sample must be continually replenished throughout the experiment. As part of the
TR&Ds, sample injectors that rapidly deliver crystals and sample solutions to the X-ray beam will be optimized
and automated during LCLS experiments along with data analysis to gauge experimental success and optimize
use of limited sample and beam time. Time resolved studies hinge on improvements to mixing injectors, laser
activation and complementary spectroscopic methods. X-ray FEL beam time is scarce so careful characterization
of samples and complex experimental setups prior to beam time is critical to ensure experimental success, in
particular for complex time resolved measurements of sensitive metalloenzymes intermediates. Experimental
design and testing, sample production, sample characterization (including spectroscopic analysis) and crystal
quality screening are supported in the laboratory, at the Stanford Synchrotron Radiation Lightsource (SSRL) and
during screening beam time at LCLS. Integrating with, and enhancing the existing programs at SSRL and LCLS,
the BTRR will provide suppo...

## Key facts

- **NIH application ID:** 10089007
- **Project number:** 1P41GM139687-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Sebastien Boutet
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,594,586
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10089007

## Citation

> US National Institutes of Health, RePORTER application 10089007, Structural Dynamics at LCLS (1P41GM139687-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10089007. Licensed CC0.

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