Exploring alternate states and oligomerization preferences of coiled‐coils by de novo structure modeling
Abstract
Homomeric coiled‐coils can self‐assemble into a wide range of structural states with different helix topologies and oligomeric states. In this study, we have combined de novo structure modeling with stability calculations to simultaneously predict structure and oligomeric states of homomeric coiled‐coils. For dimers an asymmetric modeling protocol was developed. Modeling without symmetry constraints showed that backbone asymmetry is important for the formation of parallel dimeric coiled‐coils. Collectively, our results demonstrate that high‐resolution structure of coiled‐coils, as well as parallel and antiparallel orientations of dimers and tetramers, can be accurately predicted from sequence. De novo modeling was also used to generate models of competing oligomeric states, which were used to compare stabilities and thus predict the native stoichiometry from sequence. In a benchmark set of 33 coiled‐coil sequences, forming dimers to pentamers, up to 70% of the oligomeric states could be correctly predicted. The calculations demonstrated that the free energy of helix folding could be an important factor for determining stability and oligomeric state of homomeric coiled‐coils. The computational methods developed here should be broadly applicable to studies of sequence‐structure relationships in coiled‐coils and the design of higher order assemblies with improved oligomerization specificity. Proteins 2015; 83:235–247. © 2014 Wiley Periodicals, Inc.
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MM-PBSA and MM-GBSA, which are based on molecular dynamics simulations, offer an alternative route for computing the binding free energies of protein-protein systems including coiled-coil complexes.
“Methods such as MM-PBSA and MM-GBSA,46,47 which are based on molecular dynamics (MD) simulations, offer an alternative route for computing the binding free energies of protein–protein systems48−50 including coiled-coil complexes.42,51,52”
From Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints (2025) · cites this paper as [42]
Further studies expanded predictions to higher order oligomerization states (up to pentamers) and alternative topologies.
“Further studies expanded predictions to higher order oligomerization states (up to pentamers) and alternative topologies.40−42”
From Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints (2025) · cites this paper as [42]
In the protocol, WT-metaD simulations with Boresch restraints are run on fully folded α-helices, and the cost of folding each helix is implicitly accounted for by dividing the association free energy by the number of helices in the assembly.
“In our protocol, WT-metaD simulations with Boresch restraints are ran on fully folded α-helices, and the cost of folding each helix is implicitly accounted for by dividing the association free energy by the number of helices in the assembly, similar to approaches followed by Ramos et al. and Rämisch et al.40,42”
From Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints (2025) · cites this paper as [42]
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- Authors
- Rämisch, S., Lizatović, R., & André, I.
- Affiliations
- Lund University (SE)
- Corresponding author
- André, Ingemar
- Venue
- Proteins: Structure, Function, and Bioinformatics
- Publisher
- Wiley
- Published
- 2014-12-18
- Volume
- 83
- Issue
- 2
- Pages
- 235-247
- ISSN
- 0887-3585 (ISSN-L)
- 1097-0134
- OpenAlex
- W1717107635
- Cited by
- 24
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2021: 3 · 2020: 3 · 2018: 6 · 2017: 6 · 2016: 2 · 2015: 1
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Proteins Structure Function and Bioinformatics (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Swedish Research Council
- 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 › Chemical Synthesis and Analysis
- Keywords
- coiled coil, tetramer, structural stability, sequence-structure relationship
- MeSH terms
- Amino Acid Sequence, Models, Molecular, Proteins, Thermodynamics, Protein Structure, Secondary, Protein Multimerization
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