Quantum physics in proteins
Artificial intelligence affords unprecedented insights into how
biomolecules work

Date:
November 3, 2021
Source:
Deutsches Elektronen-Synchrotron DESY
Summary:
A new analytical technique is able to provide hitherto unattainable
insights into the extremely rapid dynamics of biomolecules. The
team of developers is presenting its clever combination of quantum
physics and molecular biology. The scientists used the technique
to track the way in which the photoactive yellow protein (PYP)
undergoes changes in its structure in less than a trillionth of
a second after being excited by light.



FULL STORY ==========================================================================
A new analytical technique is able to provide hitherto unattainable
insights into the extremely rapid dynamics of biomolecules. The
team of developers, led by Abbas Ourmazd from the University of Wisconsin-Milwaukee and Robin Santra from DESY, is presenting its clever combination of quantum physics and molecular biology in the scientific
journal Nature. The scientists used the technique to track the way in
which the photoactive yellow protein (PYP) undergoes changes in its
structure in less than a trillionth of a second after being excited
by light.


==========================================================================
"In order to precisely understand biochemical processes in nature, such as photosynthesis in certain bacteria, it is important to know the detailed sequence of events," Santra explains their underlying motivation. "When
light strikes photoactive proteins, their spatial structure is altered,
and this structural change determines what role a protein takes on in
nature." Until now, however, it has been almost impossible to track the
exact sequence in which structural changes occur. Only the initial and
final states of a molecule before and after a reaction can be determined
and interpreted in theoretical terms. "But we don't know exactly how
the energy and shape changes in between the two," says Santra. "It's
like seeing that someone has folded their hands, but you can't see them interlacing their fingers to do so." Whereas a hand is large enough
and the movement is slow enough for us to follow it with our eyes,
things are not that easy when looking at molecules. The energy state of
a molecule can be determined with great precision using spectroscopy; and bright X-rays for example from an X-ray laser can be used to analyse the
shape of a molecule. The extremely short wavelength of X-rays means that
they can resolve very small spatial structures, such as the positions
of the atoms within a molecule. However, the result is not an image
like a photograph, but instead a characteristic interference pattern,
which can be used to deduce the spatial structure that created it.

Bright and short X-ray flashes Since the movements are extremely rapid
at the molecular level, the scientists have to use extremely short X-ray
pulses to prevent the image from being blurred. It was only with the
advent of X-ray lasers that it became possible to produce sufficiently
bright and short X-ray pulses to capture these dynamics.

However, since molecular dynamics takes place in the realm of
quantum physics where the laws of physics deviate from our everyday
experience, the measurements can only be interpreted with the help of
a quantum-physical analysis.

A peculiar feature of photoactive proteins needs to be taken into consideration: the incident light excites their electron shell to enter
a higher quantum state, and this causes an initial change in the shape of
the molecule. This change in shape can in turn result in the excited and
ground quantum states overlapping each other. In the resulting quantum
jump, the excited state reverts to the ground state, whereby the shape
of the molecule initially remains unchanged. The conical intersection
between the quantum states therefore opens a pathway to a new spatial
structure of the protein in the quantum mechanical ground state.

The team led by Santra and Ourmazd has now succeeded for the first time
in unravelling the structural dynamics of a photoactive protein at such a conical intersection. They did so by drawing on machine learning because
a full description of the dynamics would in fact require every possible movement of all the particles involved to be considered. This quickly
leads to unmanageable equations that cannot be solved.

6000 dimensions "The photoactive yellow protein we studied consists
of some 2000 atoms," explains Santra, who is a Lead Scientist at DESY
and a professor of physics at Universita"t Hamburg. "Since every atom
is basically free to move in all three spatial dimensions, there are a
total of 6000 options for movement. That leads to a quantum mechanical
equation with 6000 dimensions -- which even the most powerful computers
today are unable to solve." However, computer analyses based on machine learning were able to identify patterns in the collective movement of
the atoms in the complex molecule. "It's like when a hand moves: there,
too, we don't look at each atom individually, but at their collective movement," explains Santra. Unlike a hand, where the possibilities
for collective movement are obvious, these options are not as easy to
identify in the atoms of a molecule. However, using this technique,
the computer was able to reduce the approximately 6000 dimensions to
four. By demonstrating this new method, Santra's team was also able
to characterise a conical intersection of quantum states in a complex
molecule made up of thousands of atoms for the first time.

The detailed calculation shows how this conical intersection forms
in four- dimensional space and how the photoactive yellow protein
drops through it back to its initial state after being excited by
light. The scientists can now describe this process in steps of a few
dozen femtoseconds (quadrillionths of a second) and thus advance the understanding of photoactive processes. "As a result, quantum physics
is providing new insights into a biological system, and biology is
providing new ideas for quantum mechanical methodology," says Santra,
who is also a member of the Hamburg Cluster of Excellence "CUI: Advanced Imaging of Matter." "The two fields are cross-fertilising each other in
the process." DESY is one of the world's leading particle accelerator
centres and investigates the structure and function of matter -- from
the interaction of tiny elementary particles and the behaviour of novel nanomaterials and vital biomolecules to the great mysteries of the
universe. The particle accelerators and detectors that DESY develops
and builds at its locations in Hamburg and Zeuthen are unique research
tools. They generate the most intense X-ray radiation in the world,
accelerate particles to record energies and open up new windows onto
the universe. DESY is a member of the Helmholtz Association, Germany's
largest scientific association, and receives its funding from the German Federal Ministry of Education and Research (BMBF) (90 per cent) and the
German federal states of Hamburg and Brandenburg (10 per cent).

========================================================================== Story Source: Materials provided by
Deutsches_Elektronen-Synchrotron_DESY. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. A. Hosseinizadeh, N. Breckwoldt, R. Fung, R. Sepehr, M. Schmidt, P.

Schwander, R. Santra, A. Ourmazd. Few-fs resolution of a photoactive
protein traversing a conical intersection. Nature, 2021 DOI:
10.1038/ 10.1038/s41586-021-04050-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211103140103.htm

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