Andrew Savinov
@biosavinov.bsky.social
Biophysicist using single-molecule & high-throughput methods to interrogate sequence-structure-function. K99 fellow at MIT w/ Gene-Wei Li and Stan Fields; PhD w/ Steve Block at Stanford.
As always, huge thanks to Gene-Wei Li with whom it was fantastic to do this work, & of course @hannes-stark.bsky.social, Felix Faltings, Regina Barzilay, and Tommi Jaakkola for the collaboration.
@MITBiology @hhmi.org (5/n)
@MITBiology @hhmi.org (5/n)
October 27, 2025 at 12:39 PM
As always, huge thanks to Gene-Wei Li with whom it was fantastic to do this work, & of course @hannes-stark.bsky.social, Felix Faltings, Regina Barzilay, and Tommi Jaakkola for the collaboration.
@MITBiology @hhmi.org (5/n)
@MITBiology @hhmi.org (5/n)
Almost all of these de novo anti-gyrase peptides were so strongly toxic that they bacteria expressing them were totally eliminated from the population – similar to the inhibitory fragments we previously discovered! We're excited about these peptides as novel antimicrobials. (4/n)
October 27, 2025 at 12:39 PM
Almost all of these de novo anti-gyrase peptides were so strongly toxic that they bacteria expressing them were totally eliminated from the population – similar to the inhibitory fragments we previously discovered! We're excited about these peptides as novel antimicrobials. (4/n)
We tested ~1800 designs experimentally in living cells alongside fragments tiling across DNA gyrase. About 20% inhibited bacterial growth, and 5.5% were specific to the designed binding mode, which we assayed by almost 1800 mutants breaking the peptide binding interfaces! (3/n)
October 27, 2025 at 12:39 PM
We tested ~1800 designs experimentally in living cells alongside fragments tiling across DNA gyrase. About 20% inhibited bacterial growth, and 5.5% were specific to the designed binding mode, which we assayed by almost 1800 mutants breaking the peptide binding interfaces! (3/n)
We previously showed protein fragments are generalizable inhibitors of protein interactions (www.pnas.org/doi/10.1073/...).
Here, show that target sites discovered by protein fragment scanning can be attacked by alternative modalities – in particular de novo peptide binders! (2/n)
Here, show that target sites discovered by protein fragment scanning can be attacked by alternative modalities – in particular de novo peptide binders! (2/n)
High-throughput discovery of inhibitory protein fragments with AlphaFold | PNAS
Peptides can bind to specific sites on larger proteins and thereby function as inhibitors
and regulatory elements. Peptide fragments of larger prot...
www.pnas.org
October 27, 2025 at 12:39 PM
We previously showed protein fragments are generalizable inhibitors of protein interactions (www.pnas.org/doi/10.1073/...).
Here, show that target sites discovered by protein fragment scanning can be attacked by alternative modalities – in particular de novo peptide binders! (2/n)
Here, show that target sites discovered by protein fragment scanning can be attacked by alternative modalities – in particular de novo peptide binders! (2/n)
This was a wonderful collaboration with @bassafras.bsky.social, Amy Keating, and Gene-Wei Li at @MITBiology.
February 5, 2025 at 1:44 PM
This was a wonderful collaboration with @bassafras.bsky.social, Amy Keating, and Gene-Wei Li at @MITBiology.