ArticleNature2011
Solution structure of a minor and transiently formed state of a T4 lysozyme mutant.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers.
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Who cites it
145 citing papers in PubMed, 301 citations in OpenAlex.
- Benchmarking AI Protein Structure Predictors Reveals a Persistent Bias in Multi-State Proteins.bioRxiv : the preprint server for biology · 2026Article
- Dissecting mechanisms of ligand binding and conformational changes in the glutamine-binding protein.eLife · 2026Article
- Accurate protein stability prediction for small domains using mega-scale experiments.bioRxiv : the preprint server for biology · 2026Article
- Making invisible excited-state structures of pro-interleukin-18 visible by combining NMR and machine learning.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Beyond structures: solution NMR as the quantitative engine of integrated structural biology.Frontiers in molecular biosciences · 2026Review
- An optimizedJournal of biomolecular NMR · 2025Article
- Spitrobot-2 advances time-resolved cryo-trapping crystallography to under 25 ms.Communications chemistry · 2025Article
- Predicting absolute protein folding stability using generative models.Protein science : a publication of the Protein Society · 2025Article
- A combined NMR and deep neural network approach for enhancing the spectral resolution of aromatic side chains in proteins.Science advances · 2024Article
- Mapping the FF domain folding pathway via structures of transiently populated folding intermediates.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- RNA binding tunes the conformational plasticity and intradomain stability of TDP-43 tandem RNA recognition motifs.Biophysical journal · 2024Article
- Kinetic Resolution of the Atomic 3D Structures Formed by Ground and Excited Conformational States in an RNA Dynamic Ensemble.Journal of the American Chemical Society · 2023Article
- Odd-even disparity in the population of slipped hairpins in RNA repeat sequences with implications for phase separation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Accelerated Enveloping Distribution Sampling (AEDS) Allows for Efficient Sampling of Orthogonal Degrees of Freedom.Journal of chemical information and modeling · 2023Article
- Protein dynamics: The future is bright and complicated!Structural dynamics (Melville, N.Y.) · 2023Article
- Automated Path Searching Reveals the Mechanism of Hydrolysis Enhancement by T4 Lysozyme Mutants.International journal of molecular sciences · 2022Article
- Ensemble origins and distance-dependence of long-range mutational effects in proteins.iScience · 2022Article
- A litmus test for classifying recognition mechanisms of transiently binding proteins.Nature communications · 2022Article
- Measuring thermodynamic preferences to form non-native conformations in nucleic acids using ultraviolet melting.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Elucidating the mechanisms underlying protein conformational switching using NMR spectroscopy.Journal of magnetic resonance open · 2022Article
85 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Proteins are inherently plastic molecules, whose function often critically depends on excursions between different molecular conformations (conformers). However, a rigorous understanding of the relation between a protein's structure, dynamics and function remains elusive. This is because many of the conformers on its energy landscape are only transiently formed and marginally populated (less than a few per cent of the total number of molecules), so that they cannot be individually characterized by most biophysical tools. Here we study a lysozyme mutant from phage T4 that binds hydrophobic molecules and populates an excited state transiently (about 1 ms) to about 3% at 25 °C (ref. 5). We show that such binding occurs only via the ground state, and present the atomic-level model of the 'invisible', excited state obtained using a combined strategy of relaxation-dispersion NMR (ref. 6) and CS-Rosetta model building that rationalizes this observation. The model was tested using structure-based design calculations identifying point mutants predicted to stabilize the excited state relative to the ground state. In this way a pair of mutations were introduced, inverting the relative populations of the ground and excited states and altering function. Our results suggest a mechanism for the evolution of a protein's function by changing the delicate balance between the states on its energy landscape. More generally, they show that our approach can generate and validate models of excited protein states.
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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.