Speaker
Description
Diffractive single-particle imaging (SPI) using X-ray free-electron
lasers (XFELs) offers a promising approach for determining protein
structures without crystallization (Neutze2000) . For successful
reconstruction thousands of diffraction images of individual proteins
have to be assembled. It has been shown with molecular dynamics
simulations that proteins carrying a dipole moment can be oriented with
external electric fields (Marklund2017) and that the computer
algorithm that sorts the diffraction images benefits from
pre-orientation (Marklund2017, Wollter2024). A general estimate of
the required minimum field strengths for sufficient orientation is still
unknown.\
Expressions for the distribution of the angle $\theta$ between the
dipole moment $\mu$ and the field $\epsilon$ were derived for 1) a
theoretical mechanical rigid rotor model (RR) of a single protein in
which no energy is transferred to inner degrees of freedom and 2) a
theoretical thermodynamic model (TM) that assumes equilibration of all
internal degrees of freedom in the protein. Molecular dynamics (MD)
simulations show similarity with RR for low fields and good agreement
with TM for higher fields, when the simulation duration is sufficiently long
for the system to reach equilibration.
Based on RR for a single protein and assuming random orientation as well
as Boltzmann-distributed rotational kinetic energy when entering the
field region, we estimate the distribution of orientation angles for an
ensemble of proteins.
To study the beneficial effect of pre-orientation we performed Enhanced
EMC (Marklund2017, Wollter2024) with thousands of simulated
diffraction pattens (Hantke2016) of proteins oriented according
to the theoretical distributions (RR ensemble, TM).
We estimate the required fields for a given dipole moment to achieve
given angular confinements and for EEMC to benefit from pre-orientation
and relate them to the dipole moments of a dataset of 60k proteins
lankar2016).
We conclude that TM is suitable to describe the distribution of angles
even for a single protein and that field strengths required to achieve
sufficient orientation for EEMC to benefit are technically feasible for
a wide range of proteins.
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