Quantitative Protein Topography Measurements by High Resolution Hydroxyl Radical Protein Footprinting Enable Accurate Molecular Model Selection

Overview

Journal Sci Rep

Specialty Science

Date 2017 Jul 5

PMID 28674401

Citations 38

Authors

Boer Xie

Amika Sood

Robert J Woods

Joshua S Sharp

Affiliations

Soon will be listed here.

Abstract

We report an integrated workflow that allows mass spectrometry-based high-resolution hydroxyl radical protein footprinting (HR-HRPF) measurements to accurately measure the absolute average solvent accessible surface area (<SASA>) of amino acid side chains. This approach is based on application of multi-point HR-HRPF, electron-transfer dissociation (ETD) tandem MS (MS/MS) acquisition, measurement of effective radical doses by radical dosimetry, and proper normalization of the inherent reactivity of the amino acids. The accuracy of the resulting <SASA> measurements was tested by using well-characterized protein models. Moreover, we demonstrated the ability to use <SASA> measurements from HR-HRPF to differentiate molecular models of high accuracy (<3 Å backbone RMSD) from models of lower accuracy (>4 Å backbone RMSD). The ability of <SASA> data from HR-HRPF to differentiate molecular model quality was found to be comparable to that of <SASA> data obtained from X-ray crystal structures, indicating the accuracy and utility of HR-HRPF for evaluating the accuracy of computational models.

Citing Articles

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Protein shape sampled by ion mobility mass spectrometry consistently improves protein structure prediction.

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Simulation of Energy-Resolved Mass Spectrometry Distributions from Surface-Induced Dissociation.

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