TY - JOUR

T1 - PSX, Protein-Solvent Exchange

T2 - software for calculation of deuterium-exchange effects in small-angle neutron scattering measurements from protein coordinates

AU - Pedersen, Martin Cramer

AU - Wang, Yong

AU - Tidemand, Frederik Grønbæk

AU - Martel, A.

AU - Lindorff-Larsen, Kresten

AU - Arleth, Lise

PY - 2019

Y1 - 2019

N2 - Recent developments in neutron scattering instrumentation and sample handling have enabled studies of more complex biological samples and measurements at shorter exposure times. The experiments are typically conducted in D2O-based buffers to emphasize or diminish scattering from a particular component or to minimize background noise in the experiment. To extract most information from such experiments it is thus desirable to determine accurate estimates of how and when closely bound hydrogen atoms from the biomolecule exchange with the deuterium in the solvent. This article introduces and documents software, PSX, for exploring the effect of hydrogen-deuterium exchange for proteins solubilized in D2O as well as the underlying bioinformatical models. The software aims to be generally applicable for any atomistic structure of a protein and its surrounding environment, and thus captures effects of both heterogenous exchange rates throughout the protein structure and varying the experimental conditions such as pH and temperature. The paper concludes with examples of applications and estimates of the effect in typical scenarios emerging in small-angle neutron scattering on biological macromolecules in solution. The analysis presented here suggests that the common assumption of 90% exchange is in many cases an overestimate with the rapid sample handling systems currently available, which leads to fitting and calibration issues when analysing the data. Source code for the presented software is available from an online repository in which it is published under version 3 of the GNU publishing licence.

AB - Recent developments in neutron scattering instrumentation and sample handling have enabled studies of more complex biological samples and measurements at shorter exposure times. The experiments are typically conducted in D2O-based buffers to emphasize or diminish scattering from a particular component or to minimize background noise in the experiment. To extract most information from such experiments it is thus desirable to determine accurate estimates of how and when closely bound hydrogen atoms from the biomolecule exchange with the deuterium in the solvent. This article introduces and documents software, PSX, for exploring the effect of hydrogen-deuterium exchange for proteins solubilized in D2O as well as the underlying bioinformatical models. The software aims to be generally applicable for any atomistic structure of a protein and its surrounding environment, and thus captures effects of both heterogenous exchange rates throughout the protein structure and varying the experimental conditions such as pH and temperature. The paper concludes with examples of applications and estimates of the effect in typical scenarios emerging in small-angle neutron scattering on biological macromolecules in solution. The analysis presented here suggests that the common assumption of 90% exchange is in many cases an overestimate with the rapid sample handling systems currently available, which leads to fitting and calibration issues when analysing the data. Source code for the presented software is available from an online repository in which it is published under version 3 of the GNU publishing licence.

KW - bioinformatics

KW - biophysical samples

KW - hydrogen/deuterium exchange

KW - small-angle neutron scattering

KW - solvent exposure

U2 - 10.1107/S1600576719012469

DO - 10.1107/S1600576719012469

M3 - Journal article

AN - SCOPUS:85075799807

VL - 52

SP - 1427

EP - 1436

JO - Journal of Applied Crystallography

JF - Journal of Applied Crystallography

SN - 0021-8898

IS - 6

ER -