To study nanostructures in real environments, Berkeley
Lab scientists have combined theoretical and experimental approaches to
glimpse into a protein’s interaction with simple salts in water. Enabled
by x-ray absorption simulation software developed at Berkeley Lab’s Molecular
Foundry, these findings shed new light on how salts impact protein structure
at the atomic level.
Traditional crystallographic techniques, such as x-ray diffraction, provide
a profile of ordered materials with static structures. However, for dynamic
or complex systems in which the atomic structure is rapidly changing, more sophisticated
methods are needed. Now, Berkeley Lab scientists have applied x-ray absorption
spectroscopy to study a model protein, triglycine – a short chain of three
molecules of the simplest amino acid, glycine. By simulating this molecule’s
x-ray absorption spectrum the team has show how its chain kinks and straightens
in response to ions in solution.
“Watching a molecule in solution is like watching a marionette—you
can see it bending in response to making and breaking of hydrogen bonds,”
said David Prendergast, a staff scientist in the Theory of Nanostructures Facility
at the Molecular Foundry. “A concrete knowledge of how ions influence
this behavior comes from using molecular dynamics simulations, which show persistent
differences in structure on nanosecond timescales. From this data we can generate
x-ray absorption spectra which can then be compared with experimental results.”
In a specialized x-ray absorption experiment called near edge x-ray absorption
fine structure (NEXAFS), x-rays are used to probe the chemical bonding and environment
of specific elements in a molecule or nanostructure, such as the nitrogen atoms
in a triglycine molecule. Coupled with a liquid microjet technology developed
at Berkeley Labs, NEXAFS has been previously used to examine how proteins dissolve
and crystallize in the presence of various ions .
Prendergast’s software can now simulate NEXAFS data by averaging a series
of snapshots taken from a molecular dynamics simulation of a given molecule.
This software is a critical tool for interpreting NEXAFS data from complex,
dynamic systems, as the probe times in these measurements are too slow—seconds
rather than nanoseconds—to reveal structural differences at the nanoscale.
“Previous studies from our group have shown the development of x-ray
absorption spectroscopy of liquid microjets provides a new atom-sensitive probe
of the interactions between aqueous ions, but it is the advent of this new theory
that provides the first reliable molecular-level interpretation of these data,”
said Richard Saykally, a Berkeley Lab chemist and professor of chemistry at
the University of California at Berkeley. “Here we see this new combination
of theory and experiment applied to one of the most important problems in biophysical
Prendergast says his molecular dynamics technique can be used to model x-ray
spectra of a biological system with known structure to determine its local interactions,
what causes it to form a particular structure, and why it takes on a particular
conformation—all by simulating the spectra of a series of individual snapshots
and comparing with experimental results. These simulations are computationally
intensive and rely heavily on the large-scale supercomputing infrastructure
provided by Berkeley Lab’s National Energy Research Scientific Computing
“Although these effects are a fundamental part of nature, they are still
poorly understood,” said Craig Schwartz, a researcher working with Prendergast
and Saykally, whose graduate work led to this publication. “The experimental
sensitivity of NEXAFS, coupled with a breakthrough in theory, gave us new insight
into how these molecules interact.”
The researchers anticipate demand from other groups exploring water (or other
solvent) interactions, as well as both soft materials (such as polymers) and
inorganic materials (oxides and metal surfaces) that are directly relevant to
energy-related applications in catalysis, battery technology and photovoltaics.
In addition, as x-ray free electron laser sources become available to scientists,
a richer experimental data set will be available to augment theoretical findings.
A paper reporting this research titled, “Investigation of protein conformation
and interactions with salts via X-ray absorption spectroscopy,” appears
in Proceedings of the National Academy of Sciences and is available to subscribers
online. Co-authoring the paper with Schwartz, Prendergast and Saykally were
Janel Uejio, Andrew Duffin, Alice England and Daniel Kelly.
This work at the Molecular Foundry and Advanced Light Source was supported
by DOE’s Office of Science. Computational resources were provided by NERSC,
a DOE advanced scientific computing research user facility.
The Molecular Foundry is one of the five DOE Nanoscale Science Research Centers
(NSRCs), national user facilities for interdisciplinary research at the nanoscale,
supported by the DOE Office of Science. Together the NSRCs comprise a suite
of complementary facilities that provide researchers with state-of-the-art capabilities
to fabricate, process, characterize and model nanoscale materials, and constitute
the largest infrastructure investment of the National Nanotechnology Initiative.
The NSRCs are located at DOE’s Argonne, Brookhaven, Lawrence Berkeley,
Oak Ridge and Sandia and Los Alamos National Laboratories. For more information
about the DOE NSRCs, please visit http://nano.energy.gov.
Berkeley Lab is a U.S. Department of Energy national laboratory located in
Berkeley, California. It conducts unclassified scientific research and is managed
by the University of California. Visit our website at http://www.lbl.gov.