ArticleNature communications2016
Modelling proteins' hidden conformations to predict antibiotic resistance.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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.
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.
Who cites it
82 citing papers in PubMed, 143 citations in OpenAlex.
- Recommendations and considerations for hydroxyl radical protein footprinting-mass spectrometry.Nature methods · 2026Review
- Decrypting cryptic pockets with physics-based simulations and artificial intelligence.Current opinion in structural biology · 2026Review
- Unfreezing structural biology for drug discovery.Nature chemical biology · 2026Review
- Dynamic signature of activity-stability tradeoff in lactamase evolution.Nature communications · 2026Article
- Building multiscale Markov state models by systematic mapping of temporal communities.Bioinformatics (Oxford, England) · 2026Article
- 5-Hydroxylysine Captures the Suicidally-Inactivated Conformational State of Lysine 5,6-Aminomutase.International journal of molecular sciences · 2025Article
- Opening and closing of a cryptic pocket in VP35 toggles it between two different RNA-binding modes.eLife · 2025Article
- Considering Metabolic Context in Enzyme Evolution and Design.Biochemistry · 2025Review
- Discovering cryptic pocket opening and binding of a stimulant derivative in a vestibular site of the 5-HTScience advances · 2025Article
- Mass Spectrometry-Based Protein Footprinting for Protein Structure Characterization.Accounts of chemical research · 2025Article
- Symmetry-adapted Markov state models of closing, opening, and desensitizing in α 7 nicotinic acetylcholine receptors.Nature communications · 2024Article
- Friends and relatives: insight into conformational regulation from orthologues and evolutionary lineages using KIF and KIN.Faraday discussions · 2024Article
- Toward physics-based precision medicine: Exploiting protein dynamics to design new therapeutics and interpret variants.Protein science : a publication of the Protein Society · 2024Review
- Homologous mutations in human β, embryonic, and perinatal muscle myosins have divergent effects on molecular power generation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Human PLCG2 haploinsufficiency results in a novel natural killer cell immunodeficiency.The Journal of allergy and clinical immunology · 2024Article
- Loop dynamics and the evolution of enzyme activity.Nature reviews. Chemistry · 2023Review
- Folding@home: Achievements from over 20 years of citizen science herald the exascale era.Biophysical journal · 2023Review
- Stabilization of pre-existing neurotensin receptor conformational states by β-arrestin-1 and the biased allosteric modulator ML314.Nature communications · 2023Article
- Exploiting conformational dynamics to modulate the function of designed proteins.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Characterization of a Class A β-Lactamase fromACS bio & med chem Au · 2023Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
TEM β-lactamase confers bacteria with resistance to many antibiotics and rapidly evolves activity against new drugs. However, functional changes are not easily explained by differences in crystal structures. We employ Markov state models to identify hidden conformations and explore their role in determining TEM's specificity. We integrate these models with existing drug-design tools to create a new technique, called Boltzmann docking, which better predicts TEM specificity by accounting for conformational heterogeneity. Using our MSMs, we identify hidden states whose populations correlate with activity against cefotaxime. To experimentally detect our predicted hidden states, we use rapid mass spectrometric footprinting and confirm our models' prediction that increased cefotaxime activity correlates with reduced Ω-loop flexibility. Finally, we design novel variants to stabilize the hidden cefotaximase states, and find their populations predict activity against cefotaxime in vitro and in vivo. Therefore, we expect this framework to have numerous applications in drug and protein design.
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What OpenQuestion holds
Registered trials
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.