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Record W4409313764 · doi:10.1101/2025.04.07.643449

Engineering IspH for Enhanced Terpenoid Yield: Computational and Molecular Dynamics Studies

2025· preprint· en· W4409313764 on OpenAlexaff
Ashish Runthala, Venkatramanan Varadharajan, Silambarasan Tamil Selvan, Manmohan D. Sharma, Nameet Kaur, Suresh Chandra Phulara, Hazem K Ghneim

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPlant biochemistry and biosynthesis
Canadian institutionsOpal-Rt Technologies (Canada)
Fundersnot available
KeywordsTerpenoidMolecular dynamicsYield (engineering)Dynamics (music)ChemistryBiological systemBiochemical engineeringComputer scienceComputational chemistryPhysicsEngineeringBiologyStereochemistryThermodynamics

Abstract

fetched live from OpenAlex

Abstract Terpenoids play a vital role in pharmaceuticals, biofuels, and various industries, and they are produced through the methylerythritol phosphate (MEP) pathway, with IspH catalyzing the final step. This study explores IspH homologs in Bacillus and other bacteria to aid in enzyme engineering. Sequence analysis showed a conservation range of 46-79%. Phylogenetic analysis (log-likelihood -71,581.08, bootstrap 80-100) validated the evolutionary relationships. Structural modeling revealed conserved functional motifs. Molecular docking indicated HMBPP binding affinities between -4.9 and -6.4 kcal/mol, while molecular dynamics simulations confirmed the stability of the complex (RMSD 2.02-3.45 Å, Rg 21.56-22.06 Å, with a decrease in SASA upon binding). Significant hydrogen bonds were noted with His131, Asn227, and Ser271. This thorough analysis of IspH conservation, structure, and stability, along with co-evolving residue networks, underscores the potential of Bacillus IspH variants for improved terpenoid production and lays the groundwork for targeted enzyme engineering.

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.011
Threshold uncertainty score0.022

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.009
GPT teacher head0.223
Teacher spread0.214 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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