# New Tools for Experimental Phasing of Twinned Diffraction Data

> **NIH NIH R21** · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · 2020 · $301,401

## Abstract

Summary
Crystallography is an indispensable tool in modern structural biology, allowing for precise
determination of molecular interactions in proteins. The majority of the computational
crystallographic tools available have been developed on the prerequisite that the diffraction data
is free from pathologies such as twinning. For the detection of twinned data and refinement of
structures, excellent software is already available, but for more upstream tasks, no general‐
purpose tools are available. The absence of tools that allow handling of twinned data has resulted
in practical difficulties when solving structures from such data. This proposal addresses this
critical gap by developing twinning‐aware tools and algorithms for all mainstream
crystallographic tasks for which no such tools exist. We propose to adopt and extend existing
density modification and heavy atom determination methods such that they are suited for
handling twinned data. The proposed algorithm propagates vital prior information from real
space all the way into data space, numerically stabilizing an otherwise ill‐conditioned detwinning
step using a regularization approach. To provide the community with a full complement of tools
for de novo phasing, heavy atom refinement and phasing strategies will be addressed by
developing and evaluating numerical techniques needed for the twinned‐SAD likelihood
function. This problem will be addressed using an adaptive quadrature approach.

## Key facts

- **NIH application ID:** 10022493
- **Project number:** 5R21GM129649-02
- **Recipient organization:** UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
- **Principal Investigator:** Petrus H Zwart
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $301,401
- **Award type:** 5
- **Project period:** 2019-09-23 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022493

## Citation

> US National Institutes of Health, RePORTER application 10022493, New Tools for Experimental Phasing of Twinned Diffraction Data (5R21GM129649-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10022493. Licensed CC0.

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