Evidence map›Paper›PMID 37726313›Full record

ArticleScientific reports2023

A probabilistic view of protein stability, conformational specificity, and design.

Jacob A Stern, Tyler J Free, Kimberlee L Stern, Spencer Gardiner, Nicholas A Dalley, Bradley C Bundy, Joshua L Price, David Wingate, Dennis Della Corte

Abstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 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

9 authors.

Jacob A SternDepartment of Computer Science, Brigham Young University, Provo, UT, USA.
Tyler J FreeDepartment of Chemical Engineering, Brigham Young University, Provo, UT, USA.
Kimberlee L SternDepartment of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
Spencer GardinerDepartment of Physics and Astronomy, Brigham Young University, Provo, UT, USA.
Nicholas A DalleyDepartment of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
Bradley C BundyDepartment of Chemical Engineering, Brigham Young University, Provo, UT, USA.
Joshua L PriceDepartment of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
David WingateDepartment of Computer Science, Brigham Young University, Provo, UT, USA.
Dennis Della CorteDepartment of Physics and Astronomy, Brigham Young University, Provo, UT, USA. dennis.dellacorte@byu.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Various approaches have used neural networks as probabilistic models for the design of protein sequences. These "inverse folding" models employ different objective functions, which come with trade-offs that have not been assessed in detail before. This study introduces probabilistic definitions of protein stability and conformational specificity and demonstrates the relationship between these chemical properties and the [Formula: see text] Boltzmann probability objective. This links the Boltzmann probability objective function to experimentally verifiable outcomes. We propose a novel sequence decoding algorithm, referred to as "BayesDesign", that leverages Bayes' Rule to maximize the [Formula: see text] objective instead of the [Formula: see text] objective common in inverse folding models. The efficacy of BayesDesign is evaluated in the context of two protein model systems, the NanoLuc enzyme and the WW structural motif. Both BayesDesign and the baseline ProteinMPNN algorithm increase the thermostability of NanoLuc and increase the conformational specificity of WW. The possible sources of error in the model are analyzed.

Indexed as

AlgorithmsAmino Acid SequenceBayes TheoremLikelihood FunctionsProtein Stability

Identifiers

PMID37726313
PMCPMC10509192

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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.