New OpenFold3 preview out! (OF3p2)
It closes the gap to AlphaFold3 for most modalities.
Most critically, we're releasing everything, including training sets & configs, making OF3p2 the only current AF3-based model that is functionally trainable & reproducible from scratchπ§΅1/9
Iβm excited to share my first peer-reviewed publication, and my first first-author paper, "Time in mind: a multidisciplinary review on temporal perception, cognition, and memory" is now published open access in Frontiers in Cognition!
www.frontiersin.org/journals/cog... #psychology #science #time
Thank you for pointing this out. This was due to hitch in our update pipeline; ANARCI seems to number the sequence fine. This entry has now been corrected.
Predicting protein conformational flexibility remains a major challenge in structural biology. While we can now accurately model static protein structures, understanding their dynamics is still difficult, largely due to a lack of suitable training data.
Huge thanks π to my fellow members of @opig.stats.ox.ac.uk:
- our lead author Alex Greenshields-Watson
- my co-authors Fabian Spoendlin and @mcagiada.bsky.social
- and our extraordinary P.I. Charlotte Deane!
Have questions or thoughts? Letβs discuss! π§¬
The future of antibody design is bright, and weβre excited to contribute to it! π
Check out the paper for full details!
They also give rise to probabilistic metrics (e.g. conformational likelihoods) that could better reflect state occupancies and outperform current metrics as ranking and filtering criteria.
Plus, generative models open the door to robust, antigen-conditional de novo design. π
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We also suggest generative approaches (like diffusion or flow matching) can help!
Hereβs why:
β’ They target conformational distributions directly as the learning objective.
β’ They sample these distributions efficiently.
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We call for:
π§ More ML-grade unbound data for training predictors,
β
Better methods to rank/QC structure predictions + estimate uncertainty,
π Improved flexibility/ensemble predictions,
π¬ Carrying multiple conformations into downstream analyses.
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In other words, designing better-targeted, more reliable antibodies demands better handling of multiple conformations!
Our paper highlights these challenges, reviews current antibody structure predictors (e.g. AF3, ESM3, ABodyBuilder3), and proposes key directions for progress.
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Worse, this conformational heterogeneity directly affects antibody function!
β’ Entropic contributions influence binding and affinity (ΞG=ΞHβTΞS).
β’ Flexibility impacts many therapeutic traits.
β’ Flexibility could even be exploitedβe.g., pH-sensitive antibodies that βswitch onβ inside tumours! π§ͺ
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Therapeutic antibodies are manufactured, stored, and administered in their free (unbound) state.
So predicting that conformation is crucial! Itβs also hard:
1οΈβ£ Most antibody structures in the PDB are bound forms, leaving little unbound data.
2οΈβ£ CDR loops are flexibleβliteral moving targets!
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Itβs an exciting time in protein design! π§¬β¨ But much of the therapeutic potentialβespecially for antibodiesβremains untapped. Why? π€
Antibodies seem like ideal candidates for design! π
Hereβs a quick thread summarising our new review paper on the state of antibody structure prediction. π
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