TY  - JOUR
A1  - Mandl, Thomas
A1  - Östlin, Christofer
A1  - Dawod, Ibrahim E.
A1  - Brodmerkel, Maxim N.
A1  - Marklund, Erik G.
A1  - Martin, Andrew V.
A1  - Timneanu, Nicusor
A1  - Caleman, Carl
T1  - Structural Heterogeneity in Single Particle Imaging Using X-ray Lasers
JF  - The Journal of Physical Chemistry Letters
N2  - One of the challenges facing single particle imaging with ultrafast X-ray pulses is the structural heterogeneity of the sample to be imaged. For the method to succeed with weakly scattering samples, the diffracted images from a large number of individual proteins need to be averaged. The more the individual proteins differ in structure, the lower the achievable resolution in the final reconstructed image. We use molecular dynamics to simulate two globular proteins in vacuum, fully desolvated as well as with two different solvation layers, at various temperatures. We calculate the diffraction patterns based on the simulations and evaluate the noise in the averaged patterns arising from the structural differences and the surrounding water. Our simulations show that the presence of a minimal water coverage with an average 3 Å thickness will stabilize the protein, reducing the noise associated with structural heterogeneity, whereas additional water will generate more background noise.
KW  - Protein structure
KW  - Physical and chemical processes
KW  - Peptides and proteins
KW  - Physical and chemical properties
KW  - Layers
Y1  - 2020
VL  - 2020
IS  - Volume 11, Issue 15
SP  - 6077
EP  - 6083
ER  - 
TY  - JOUR
A1  - Mandl, Thomas
A1  - Sinelnikova, Anna
A1  - Östlin, Christofer
A1  - Grånäs, Oscar
A1  - Brodmerkel, Maxim N.
A1  - Markl, Erik G.
A1  - Caleman, Carl
T1  - Reproducibility in the unfolding process of protein induced by an external electric field
JF  - Chemical Science
N2  - The dynamics of proteins are crucial for their function. However, commonly used techniques for studying protein structures are limited in monitoring time-resolved dynamics at high resolution. Combining electric fields with existing techniques to study gas-phase proteins, such as single particle imaging using free-electron lasers and gas-phase small angle X-ray scattering, has the potential to open up a new era in time-resolved studies of gas-phase protein dynamics. Using molecular dynamics simulations, we identify well-defined unfolding pathways of a protein, induced by experimentally achievable external electric fields. Our simulations show that strong electric fields in conjunction with short-pulsed X-ray sources such as free-electron lasers can be a new path for imaging dynamics of gas-phase proteins at high spatial and temporal resolution.
KW  - Reproducibility protein
Y1  - 
ER  -