New system for archiving integrative structures

Vallat, Brinda; Webb, Benjamin; Fayazi, Maryam; Voinea, Serban; Tangmunarunkit, Hongsuda; Ganesan, Sai J.; Lawson, Catherine L.; Westbrook, John D.; Kesselman, Carl; Šali, Andrej; Berman, Helen M.

doi:10.1107/s2059798321010871

Cited by 33 publications

(25 citation statements)

References 53 publications

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“…In future, the approach could be extended to other model ensembles of coarse-grained models. Methods such as PrISM are expected to improve the utility of deposited integrative structures in the new Protein Data Bank archive for integrative structures [25], [26], [28], [29] (http://pdb-dev.wwpdb.org).…”

Section: Discussionmentioning

confidence: 99%

“…In future, the approach could be extended to other model ensembles of coarse-grained models. Methods such as PrISM are expected to improve the utility of deposited integrative structures in the PDB (http://pdb-dev.wwpdb.org) (Sali et al ., 2015, 20; Vallat et al ., 2018, 2019, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…Finally, these methods analyze structures with a small number of proteins and have not been demonstrated to be scalable for tens of thousands of models of large assemblies. [25]- [29] (http://pdbdev.wwpdb.org). Here, we demonstrate PrISM, an efficient method to visualize high and lowprecision regions of an integrative model.…”

Section: Introductionmentioning

confidence: 99%

“…Finally, these methods analyze structures with a small number of proteins and have not been demonstrated to be scalable for large ensembles of macromolecular assemblies. Validation of integrative models, including assessment of model precision, is an open research challenge and timely due to the new PDB archive for integrative structures (Sali et al, 2015;Vallat et al, 2018;Berman et al, 2019;Vallat et al, 2019Vallat et al, , 2021 (http://pdbdev.wwpdb.org). Here, we demonstrate PrISM, a method to visualize high and low-precision regions of an integrative model.…”

Section: Introductionmentioning

confidence: 99%

“…Validation of integrative models, including assessment of model precision, is an open research challenge and timely due to the new PDB archive for integrative structures (Sali et al ., 2015; Vallat et al ., 2018; Berman et al ., 2019; Vallat et al ., 2019, 2021) (http://pdb-dev.wwpdb.org). Here, we demonstrate PrISM, a method to visualize high and low-precision regions of an integrative model.…”

Section: Introductionmentioning

confidence: 99%

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PrISM: Precision for Integrative Structural Models

Kasukurthi

Viswanath

2021

Preprint

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Motivation: Integrative modeling of macromolecular structures usually results in an ensemble of models that satisfy the input information. The model precision, or variability among these models is estimated globally, i.e., a single precision value is reported for the model. However, it would be useful to identify regions of high and low precision. For instance, low-precision regions can suggest where the next experiments could be performed and high-precision regions can be used for further analysis, e.g., suggesting mutations. Results: We develop PrISM (Precision for Integrative Structural Models), using autoencoders to efficiently and accurately annotate precision for integrative models. The method is benchmarked and tested on five examples of binary protein complexes and five examples of large protein assemblies. The annotated precision is shown to be consistent with, and more informative than localization densities. The generated networks are also interpreted by gradient-based attention analysis. Availability: Source code is at https://github.com/isblab/prism.

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Section: Discussionmentioning

confidence: 99%

“…In future, the approach could be extended to other model ensembles of coarse-grained models. Methods such as PrISM are expected to improve the utility of deposited integrative structures in the PDB (http://pdb-dev.wwpdb.org) (Sali et al ., 2015, 20; Vallat et al ., 2018, 2019, 2021).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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PrISM: Precision for Integrative Structural Models

Kasukurthi

Viswanath

2021

Preprint

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The SWISS‐MODEL Repository of 3D Protein Structures and Models

Robin,

Waterhouse,

Bienert

et al. 2023

Methods and Principles in Medicinal Chemistry

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A look at the face of the molten globule: Structural model of the Helicobacter pylori apoflavodoxin ensemble at acidic pH

et al. 2022

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Molten globule (MG) is the name given to a compact, non‐native conformation of proteins that has stimulated the imagination and work in the protein folding field for more than 40 years. The MG has been proposed to play a central role in the folding reaction and in important cell functions, and to be related to the onset of misfolding diseases. Due to its inherent intractability to high‐resolution studies, atomistic structural models have not yet been obtained. We present here an integrative atomistic model of the MG formed at acidic pH by the apoflavodoxin from the human pathogen Helicobacter pylori. This MG has been previously shown to exhibit the archetypical expansion, spectroscopic and thermodynamic features of a molten conformation. To obtain the model, we have analyzed the stability of wild‐type and 55 apoflavodoxin mutants to derive experimental equilibrium Φ values that have been used in biased molecular dynamics simulations to convert the native conformation into an MG ensemble. The ensemble has been refined to reproduce the experimental hydrodynamic radius and circular dichroism (CD) spectrum. The refined ensemble, deposited in PDB‐Dev, successfully explains the characteristic 1H‐nuclear magnetic resonance (NMR) and near‐UV CD spectral features of the MG as well as its solvent‐accessible surface area (SASA) change upon unfolding. This integrative model of an MG will help to understand the energetics and roles of these elusive conformations in protein folding and misfolding. Interestingly, the apoflavodoxin MG is structurally unrelated to previously described partly unfolded conformations of this protein, exemplifying that equilibrium MGs need not to reflect the properties of kinetic intermediates.

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New system for archiving integrative structures

Cited by 33 publications

References 53 publications

PrISM: Precision for Integrative Structural Models

PrISM: Precision for Integrative Structural Models

The SWISS‐MODEL Repository of 3D Protein Structures and Models

A look at the face of the molten globule: Structural model of the Helicobacter pylori apoflavodoxin ensemble at acidic pH

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