Hekstra Lab
@hekstralab.bsky.social
Enabling better crystal structures & better structure prediction. Can’t wait to see where folks take that! SFCalculator is implemented in PyTorch, TensorFlow, and JAX. Open Source. See biorxiv.org/content/10.1... for more info & github.com/Hekstra-Lab/... to get started. 4/4
February 23, 2025 at 1:52 AM
Enabling better crystal structures & better structure prediction. Can’t wait to see where folks take that! SFCalculator is implemented in PyTorch, TensorFlow, and JAX. Open Source. See biorxiv.org/content/10.1... for more info & github.com/Hekstra-Lab/... to get started. 4/4
With SFCalculator you can also *train* structure prediction / generative models directly on X-ray data. As
James Holton has shown, the data are much more accurate than the models. The result: experiment-based generative models for ensembles (not yet general!) 3/4
James Holton has shown, the data are much more accurate than the models. The result: experiment-based generative models for ensembles (not yet general!) 3/4
February 23, 2025 at 1:52 AM
With SFCalculator you can also *train* structure prediction / generative models directly on X-ray data. As
James Holton has shown, the data are much more accurate than the models. The result: experiment-based generative models for ensembles (not yet general!) 3/4
James Holton has shown, the data are much more accurate than the models. The result: experiment-based generative models for ensembles (not yet general!) 3/4
We can refine protein structures by searching the latent space of pre-trained generative models. Using a Boltzmann Generator (@franknoe) as an example, doing so yields models with good physics & data fit! 2/4
February 23, 2025 at 1:52 AM
We can refine protein structures by searching the latent space of pre-trained generative models. Using a Boltzmann Generator (@franknoe) as an example, doing so yields models with good physics & data fit! 2/4
Fruit of a close collaboration with Rama Ranganathan's group, where Doeke, Ian (@kiwhite), and Rama first developed EFX, and BoRam worked tirelessly to grow crystals and analyze data. New hardware and software from @HekstraLab were critical for success!
February 23, 2025 at 1:46 AM
Fruit of a close collaboration with Rama Ranganathan's group, where Doeke, Ian (@kiwhite), and Rama first developed EFX, and BoRam worked tirelessly to grow crystals and analyze data. New hardware and software from @HekstraLab were critical for success!
In evolution, members of a protein family are often variations on a theme. The dynamic states resemble stable states of other channels: The sequence of steps of ion permeation is conserved from channel to channel with variations in relative energy. 7/8
February 23, 2025 at 1:46 AM
In evolution, members of a protein family are often variations on a theme. The dynamic states resemble stable states of other channels: The sequence of steps of ion permeation is conserved from channel to channel with variations in relative energy. 7/8
Does the channel itself move? Yes! It moves as the ions pass, differently depending on the direction of ion flow. This suggests how rectification (asymmetric currents) can evolve. 6/8
February 23, 2025 at 1:46 AM
Does the channel itself move? Yes! It moves as the ions pass, differently depending on the direction of ion flow. This suggests how rectification (asymmetric currents) can evolve. 6/8
What do we see? K+ ions coming in, hopping, and leaving. We see the K+ ions move, putting on a new “coat” of water molecules as they exit. 5/8
February 23, 2025 at 1:46 AM
What do we see? K+ ions coming in, hopping, and leaving. We see the K+ ions move, putting on a new “coat” of water molecules as they exit. 5/8
The experiment in simple: a crystal between two electrodes; X-rays coming in from the side: 4/8
February 23, 2025 at 1:46 AM
The experiment in simple: a crystal between two electrodes; X-rays coming in from the side: 4/8
Crystals of NaK2K, (H/T Youxing Jiang @ UTSW), form an ideal starting point: all ion channel pores are easily aligned with electric field (E): half of them “up”, half “down”. The red spheres are K+ ions: 3/8
February 23, 2025 at 1:46 AM
Crystals of NaK2K, (H/T Youxing Jiang @ UTSW), form an ideal starting point: all ion channel pores are easily aligned with electric field (E): half of them “up”, half “down”. The red spheres are K+ ions: 3/8
Key is EF-X, a technique in which we apply electric field (EF) pulses to protein crystals and see the resulting motions with X-ray pulses. Physiological electric field, temperature, and timescales are all accessible. 2/8
February 23, 2025 at 1:46 AM
Key is EF-X, a technique in which we apply electric field (EF) pulses to protein crystals and see the resulting motions with X-ray pulses. Physiological electric field, temperature, and timescales are all accessible. 2/8
Led by Rick Hewitt and Kevin Dalton, the result is Laue-DIALS, hosted by @rs-station.bsky.social at rs-station.github.io/laue-dials/. Wanna try this out but need advice? Please get in touch. Further upgrades coming soon! Read more at pubs.aip.org/aca/sdy/arti... 2/2
Laue-DIALS: Open-source software for polychromatic x-ray diffraction data
Most x-ray sources are inherently polychromatic. Polychromatic (“pink”) x-rays provide an efficient way to conduct diffraction experiments as many more photons
pubs.aip.org
February 23, 2025 at 1:36 AM
Led by Rick Hewitt and Kevin Dalton, the result is Laue-DIALS, hosted by @rs-station.bsky.social at rs-station.github.io/laue-dials/. Wanna try this out but need advice? Please get in touch. Further upgrades coming soon! Read more at pubs.aip.org/aca/sdy/arti... 2/2