Evidence map›Paper›PMID 38568188›Full record

ArticleACS synthetic biology2024

Combining Rosetta Sequence Design with Protein Language Model Predictions Using Evolutionary Scale Modeling (ESM) as Restraint.

Moritz Ertelt, Jens Meiler, Clara T Schoeder

Abstract read
In one paragraph

Article in ACS synthetic biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Moritz ErteltInstitute for Drug Discovery, University Leipzig Medicine Faculty, Liebigstr. 19, D-04103 Leipzig, Germany.ORCID 0009-0004-2506-6660
Jens MeilerInstitute for Drug Discovery, University Leipzig Medicine Faculty, Liebigstr. 19, D-04103 Leipzig, Germany.
Clara T SchoederInstitute for Drug Discovery, University Leipzig Medicine Faculty, Liebigstr. 19, D-04103 Leipzig, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Computational protein sequence design has the ambitious goal of modifying existing or creating new proteins; however, designing stable and functional proteins is challenging without predictability of protein dynamics and allostery. Informing protein design methods with evolutionary information limits the mutational space to more native-like sequences and results in increased stability while maintaining functions. Recently, language models, trained on millions of protein sequences, have shown impressive performance in predicting the effects of mutations. Assessing Rosetta-designed sequences with a language model showed scores that were worse than those of their original sequence. To inform Rosetta design protocols with language model predictions, we added a new metric to restrain the energy function during design using the Evolutionary Scale Modeling (ESM) model. The resulting sequences have better language model scores and similar sequence recovery, with only a minor decrease in the fitness as assessed by Rosetta energy. In conclusion, our work combines the strength of recent machine learning approaches with the Rosetta protein design toolbox.

Indexed as

ProteinsAmino Acid SequenceProteinscomputational protein designde novo proteinsevolutionary fitnessprotein language modelprotein language modelsRosettathermodynamic stability

Identifiers

PMID38568188
PMCPMC11036486

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.