Title: Reconstruction from limited single-particle diffraction data via simultaneous determination of state, orientation, intensity, and phase

Abstract

Free-electron lasers now have the ability to collect X-ray diffraction patterns from individual molecules; however, each sample is delivered at unknown orientation and may be in one of several conformational states, each with a different molecular structure. Hit rates are often low, typically around 0.1%, limiting the number of useful images that can be collected. Determining accurate structural information requires classifying and orienting each image, accurately assembling them into a 3D diffraction intensity function, and determining missing phase information. Additionally, single particles typically scatter very few photons, leading to high image noise levels. We develop a multitiered iterative phasing algorithm to reconstruct structural information from singleparticle diffraction data by simultaneously determining the states, orientations, intensities, phases, and underlying structure in a single iterative procedure. We leverage real-space constraints on the structure to help guide optimization and reconstruct underlying structure from very few images with excellent global convergence properties. We show that this approach can determine structural resolution beyond what is suggested by standard Shannon sampling arguments for ideal images and is also robust to noise.

Authors:

Donatelli, Jeffrey J. ^[1]; Sethian, James A. ^[2]; Zwart, Peter H. ^[3]

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+ Show Author Affiliations

1. Department of Applied Mathematics, Lawrence Berkeley National Laboratory, Berkeley, CA 94720,, Center for Advanced Mathematics for Energy Research Applications, Lawrence Berkeley National Laboratory, Berkeley, CA 94720,
2. Department of Applied Mathematics, Lawrence Berkeley National Laboratory, Berkeley, CA 94720,, Center for Advanced Mathematics for Energy Research Applications, Lawrence Berkeley National Laboratory, Berkeley, CA 94720,, Department of Mathematics, University of California, Berkeley, CA 94720,
3. Center for Advanced Mathematics for Energy Research Applications, Lawrence Berkeley National Laboratory, Berkeley, CA 94720,, Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720

Publication Date:

Mon Jun 26 00:00:00 EDT 2017

Research Org.:

Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Advanced Scientific Computing Research (ASCR); National Institutes of Health (NIH)

OSTI Identifier:

1366768

Alternate Identifier(s):

OSTI ID: 1379908

Grant/Contract Number:  

AC02-05CH11231

Resource Type:

Published Article

Journal Name:

Proceedings of the National Academy of Sciences of the United States of America

Additional Journal Information:

Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 114 Journal Issue: 28; Journal ID: ISSN 0027-8424

Publisher:

Proceedings of the National Academy of Sciences

Country of Publication:

United States

Language:

English

Subject:

97 MATHEMATICS AND COMPUTING; structure determination; multitiered iterative phasing; single-particle imaging