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Record W4366351752 · doi:10.1093/protein/gzad004

Enzyme design pioneer Steve Mayo: I was trying to capture the fundamental physics of the problem as a way to elucidate mechanisms

2023· article· en· W4366351752 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueProtein Engineering Design and Selection · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Structure and Dynamics
Canadian institutionsUniversity of Ottawa
Fundersnot available
KeywordsLibrary scienceEnvironmental ethicsPhilosophyComputer science

Abstract

fetched live from OpenAlex

Steve Mayo is a Bren Professor of Biology and Chemistry and Merkin Institute Professor at the California Institute of Technology. He is widely recognized as a pioneer of computational protein design, having achieved the first fully automated design of a novel protein sequence that folds into its target structure1 as well as the first computational design of a biocatalyst capable of transforming a predefined organic substrate2. PEDS recently sat down with Dr Mayo to talk about his background and contributions to the development of computational enzyme design, and thoughts about the future of this field. Mayo: I was a sophomore undergraduate student at Penn State majoring in chemistry. I started working in Roy Olofson’s lab to obtain Honors credits. As part of that, I was synthesizing small molecule drugs and using X-ray crystallography to study these molecules. I became very frustrated with trying to visualize their structures using a program where you had to type in the rotation angles, and then a couple of minutes later, it would print out an image of your molecule. And of course you could never get it right. You had to spend all day trying to get this program to produce a nice image. And so I decided to take a graduate level computer science and graphics course and learn how to use an old school real-time vector graphics machine that Penn State had. As I was learning how to do computer graphics to visualize molecules in real time, I was also taking some biochemistry courses and got really fascinated with proteins. This led me to write my undergraduate thesis on a modeling program to do visualization of molecules, including proteins and nucleic acids.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.870
Threshold uncertainty score0.472

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.008
GPT teacher head0.204
Teacher spread0.196 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it