# Atomic Level Analysis of Biomolecular Structure

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $396,857

## Abstract

Atomic Level Analysis of Biomolecular Structure
The overall objective of this proposal is to develop enhanced methods for analyzing structures of
biological macromolecules at an atomic level of resolution. We build on our recent accomplishments
and worldwide experience showing that single- and multi-wavelength anomalous diffraction (SAD and
MAD) now predominate for de novo determinations of macromolecular crystal structures. We also build
on the evolution of our own efforts in high-resolution structure determination to include analyses by
cryogenic electron microscopy (cryo-EM). Our philosophy is to drive the development of methods by
the demands of compelling applications to current problems of biological significance. We propose to
optimize SAD and MAD phasing procedures and to enhance cryo-EM analyses of biomolecules at the
atomic level in the course of studies of membrane proteins, macromolecular assemblages, eukaryotic
proteins and other challenges. The overall objective is embodied in three specific aims: (1) We
propose to enhance anomalous diffraction phasing procedures for challenging problems. One focus is
on improved methods for increasing signal-to-noise ratios for anomalous diffraction by combining data
from many crystals. A second focus is on enhanced MAD procedures for accurate experimental phase
evaluation. (2) We propose to develop methods for the manipulation and diffraction analysis of
microcrystals. One focus is on intrinsically small crystals, such as those of membrane proteins grown in
lipidic cubic phase; and a second focus is on microcrystals purposed for the minimization of absorption,
as is needed for low-energy native SAD experiments, or for rapid diffusion in time-resolved
experiments. (3) We propose to enhance methods for analyzing cryo-EM structures using experience
gained in analyzing x-ray crystal structures and in validating the fittings of atomic model interpretations
to experimental EM maps.

## Key facts

- **NIH application ID:** 10246938
- **Project number:** 5R01GM107462-08
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** WAYNE A. HENDRICKSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $396,857
- **Award type:** 5
- **Project period:** 2014-06-03 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246938

## Citation

> US National Institutes of Health, RePORTER application 10246938, Atomic Level Analysis of Biomolecular Structure (5R01GM107462-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246938. Licensed CC0.

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