Hekstra Lab

Research group of Prof. Doeke Hekstra | Harvard Department of Molecular & Cellular Biology

[Alisia Fadini @FadiniAli]

You shouldn’t have to have access to a GPU in-house to run ROCKET 💸 Phenix now hosts it on a server (free for academics https://t.co/5I9KMLso41). Try phenix.rocket and reach out if you need help – this is brand new! 15/15

[Hekstra Lab @HekstraLab]

We're a big step closer to automated determination of protein structures. The key? Having AlphaFold listen to experimental data. Great work, led by @alisiafadini and @mhli41 in an inspiring collaboration with @MoAlQuraishi and Randy Read.

Here's a detailed thread by Alisia:

[Alisia Fadini @FadiniAli]

ROCKET 🚀 inference-time optimization of AlphaFold to fit structural data is published! https://t.co/uogMbJZMXs
Since our preprint, we’ve pushed it to regimes where other methods break: low resolution, weak signal, real experimental edge cases. Here’s what we learned: 1/15

[Alisia Fadini @FadiniAli]

ROCKET 🚀 inference-time optimization of AlphaFold to fit structural data is published! https://t.co/uogMbJZMXs
Since our preprint, we’ve pushed it to regimes where other methods break: low resolution, weak signal, real experimental edge cases. Here’s what we learned: 1/15

[Hekstra Lab @HekstraLab]

Running SFCalculator under the hood!

[Hekstra Lab @HekstraLab]

Can AlphaFold refine structures for X-ray & Cryo-EM/ET data? Now it can! Great collab with @MoAlQuraishi and Randy Read, led by Alisia @FadiniAli and @mhli41. Preprint: https://t.co/Ol8EJ8N6ep Summary 🧵below. Code to follow...

[Alisia Fadini @FadiniAli]

Structural biology is in an era of dynamics & assemblies but turning raw experimental data into atomic models at scale remains challenging.
@mhli41 and I present ROCKET🚀: an AlphaFold augmentation that integrates crystallographic and cryoEM/ET data with room for more! 1/14.

[Hekstra Lab @HekstraLab]

@the_kittylord David, it's not *that* bad. There is just more progress to be made!

[Hekstra Lab @HekstraLab]

@YazdizadehAli We'll (re)tweet about that soon. See https://t.co/Ol8EJ8N6ep!

[Hekstra Lab @HekstraLab]

Crystal structures are *not* God-given truth. They approximate, w/ flaws & errors, X-ray diffraction data. AlphaFold etc. have been trained on structures, not data. SFCalculator now differentiably connects structures to diffraction data. What does this enable? 🧵 1/4

[Hekstra Lab @HekstraLab]

@mhli41 @YazdizadehAli More about that coming very soon!

[Hekstra Lab @HekstraLab]

@CarreraZuriel email me at [email protected]!

[Hekstra Lab @HekstraLab]

Now in Cell: K+ ion channels enable electric currents consisting of potassium ions to generate action potentials in heart, brain, and muscle. For the first time, we can now see these currents atom-by-atom. https://t.co/PnpLhwMvGf a thread🧵 1/8

[Hekstra Lab @HekstraLab]

@CellCellPress, for completeness.

[Hekstra Lab @HekstraLab]

Led by Rick Hewitt and Kevin Dalton, the result is Laue-DIALS, hosted by @rs-station.bsky.social at https://t.co/vL9M95RkD4. Wanna try this out but need advice? Please get in touch. Further upgrades coming soon! Read more at https://t.co/H2deWH92zx 2/2

[Hekstra Lab @HekstraLab]

X-ray diffraction can access protein dynamics. Why so few datasets? One reason? Lack of powerful pulsed X-ray sources. XFELs are limited. Synchrotrons throw away >99% of photons. Working with Aaron Bewster (DIALS/LBNL) and BioCARS (https://t.co/YY3IL6fJ4x) to change this! 1/2

[Hekstra Lab @HekstraLab]

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 https://t.co/cwl1zYOz6U for more info & https://t.co/k9a3BwL3qJ to get started. 4/4

[Hekstra Lab @HekstraLab]

With SFCalculator you can also *train* structure prediction / generative models directly on X-ray data. As @JHoltonMADSci has shown, the data are much more accurate than the models. 3/4

[Hekstra Lab @HekstraLab]

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! 8/8

[Hekstra Lab @HekstraLab]

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