Developments in integrative modeling with dynamical interfaces
Abstract
Proteins are dynamic, and this holds especially for their surfaces. They display ensembles of conformations, which allows them to interact with diverse partners, often via the same patch of surface, and execute their distinct functions. Binding a specific partner can stimulate - or suppress - a distinct signaling pathway. This diversity poses a challenge: how to reliably model a specific protein-protein interaction (PPI)? This problem is compounded in protein assemblies, which are typically large, involving multiple protein-protein interfaces. Integrative modeling (IM), which combines diverse data, has emerged as the most promising strategy; however, modeling dynamical interfaces, often at the detailed level, which are at the heart of reliable predictions of assemblies, still poses a challenge. Here we review hurdles and advances in integrative modeling of dynamical interfaces; while some could have been predicted or expected, others transformed modeling in unanticipated ways. We further comment on what we believe could be possible future advances.
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Global flexibility is an important consideration for docking approaches.
“While the global flexibility (multiplicity of conformations of the overall structure), may not be a problem for a number of protein docking cases (see above), in general, it is an important consideration for the docking approaches [20].”
From Challenges in protein docking (2020) · cites this paper as [20]
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“While the global flexibility (multiplicity of conformations of the overall structure), may not be a problem for a number of protein docking cases (see above), in general, it is an important consideration for the docking approaches [20].”
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“More and more data suggest that protein interfaces are dynamic objects, sometimes including disordered, flexible segments and conformational heterogeneity [25-28], and that this aspect should also be taken into account [29-31], in particular as it plays a part in the specificity of these interactions [32].”
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Moving pictures: Reassessing docking experiments with a dynamic view of protein interfacesPreprint
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Zhang, Z., Huang, B., Zhang, X. C., & Lin, J. (2021) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2021.01.023
- Authors
- Ozdemir, E. S., Nussinov, R., Gursoy, A., & Keskin, O.
- Affiliations
- Tel Aviv University (IL)
- Venue
- Current Opinion in Structural Biology
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 56
- Pages
- 11-17
- ISSN
- 0959-440X (ISSN-L)
- OpenAlex
- W2902942225
- Cited by
- 17
- References
- 58
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 1
- FWCI
- 0.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Structural Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Frederick National Laboratory for Cancer Research, National Institutes of Health
- Intramural Research Program of NIH, Frederick National Lab, Center for Cancer Research
- TUBITAK
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- integrative modeling, protein-protein interfaces, protein-protein interaction, protein assembly, protein dynamics, conformational ensembles, protein-protein interface prediction
- MeSH terms
- Models, Molecular, Protein Conformation, Proteins, Molecular Docking Simulation
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