ArticlePLoS computational biology2015
Exposing Hidden Alternative Backbone Conformations in X-ray Crystallography Using qFit.
Article in PLoS computational biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 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
59 citing papers in PubMed.
- Putrescine-bound structure and multi-temperature crystallography provide new insights into ligand binding and conformational heterogeneity in spermidine synthase.Structural dynamics (Melville, N.Y.) · 2026Article
- Understanding how enzymes work: the journey to ensemble-function studies.The FEBS journal · 2026Review
- Unfreezing structural biology for drug discovery.Nature chemical biology · 2026Review
- Hydrogen-deuterium exchange reveals catalytically linked protein flexibility in myoglobin-mediated intramolecular C(spProtein science : a publication of the Protein Society · 2026Article
- Semi-automated modeling of reaction states in time-resolved serial femtosecond crystallography using molecular dynamics sampled conformations.Structural dynamics (Melville, N.Y.) · 2025Article
- Article
- Mapping allosteric rewiring in related protein structures from collections of crystallographic multiconformer models.bioRxiv : the preprint server for biology · 2025Article
- Expanding Automated Multiconformer Ligand Modeling to Macrocycles and Fragments.bioRxiv : the preprint server for biology · 2025Article
- Exploring the dynamics of allostery through multi-dimensional crystallography.Biophysical reviews · 2024Review
- Article
- Article
- Uncovering Protein Ensembles: Automated Multiconformer Model Building for X-ray Crystallography and Cryo-EM.bioRxiv : the preprint server for biology · 2024Article
- Alternate conformations found in protein structures implies biological functions: A case study using cyclophilin A.Current research in structural biology · 2024Article
- High-resolution double vision of the allosteric phosphatase PTP1B.Acta crystallographica. Section F, Structural biology communications · 2024Article
- Design of efficient artificial enzymes using crystallographically-enhanced conformational sampling.bioRxiv : the preprint server for biology · 2023Article
- Emerging Time-Resolved X-Ray Diffraction Approaches for Protein Dynamics.Annual review of biophysics · 2023Review
- FLEXR: automated multi-conformer model building using electron-density map sampling.Acta crystallographica. Section D, Structural biology · 2023Article
- Temporal and spatial resolution of distal protein motions that activate hydrogen tunneling in soybean lipoxygenase.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Obtaining anomalous and ensemble information from protein crystals from 220 K up to physiological temperatures.Acta crystallographica. Section D, Structural biology · 2023Article
- Refinement of multiconformer ensemble models from multi-temperature X-ray diffraction data.Methods in enzymology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Proteins must move between different conformations of their native ensemble to perform their functions. Crystal structures obtained from high-resolution X-ray diffraction data reflect this heterogeneity as a spatial and temporal conformational average. Although movement between natively populated alternative conformations can be critical for characterizing molecular mechanisms, it is challenging to identify these conformations within electron density maps. Alternative side chain conformations are generally well separated into distinct rotameric conformations, but alternative backbone conformations can overlap at several atomic positions. Our model building program qFit uses mixed integer quadratic programming (MIQP) to evaluate an extremely large number of combinations of sidechain conformers and backbone fragments to locally explain the electron density. Here, we describe two major modeling enhancements to qFit: peptide flips and alternative glycine conformations. We find that peptide flips fall into four stereotypical clusters and are enriched in glycine residues at the n+1 position. The potential for insights uncovered by new peptide flips and glycine conformations is exemplified by HIV protease, where different inhibitors are associated with peptide flips in the "flap" regions adjacent to the inhibitor binding site. Our results paint a picture of peptide flips as conformational switches, often enabled by glycine flexibility, that result in dramatic local rearrangements. Our results furthermore demonstrate the power of large-scale computational analysis to provide new insights into conformational heterogeneity. Overall, improved modeling of backbone heterogeneity with high-resolution X-ray data will connect dynamics to the structure-function relationship and help drive new design strategies for inhibitors of biomedically important systems.
Indexed as
Identifiers
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.