SOP-MULTI: A Self-Organized Polymer-Based Coarse-Grained Model for Multidomain and Intrinsically Disordered Proteins with Conformation Ensemble Consistent with Experimental Scattering Data
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Abstract
Multidomain proteins with long flexible linkers and full-length intrinsically disordered proteins (IDPs) are best defined as an ensemble of conformations rather than a single structure. Determining high-resolution ensemble structures of such proteins poses various challenges by using tools from experimental structural biophysics. Integrative approaches combining available low-resolution ensemble-averaged experimental data and in silico biomolecular reconstructions are now often used for the purpose. However, extensive Boltzmann weighted conformation sampling for large proteins, especially for ones where both the folded and disordered domains exist in the same polypeptide chain, remains a challenge. In this work, we present a 2-site per amino-acid resolution SOP-MULTI force field for simulating coarse-grained models of multidomain proteins. SOP-MULTI combines two well-established self-organized polymer models─: (i) SOP-SC models for folded systems and (ii) SOP-IDP for IDPs. For the SOP-MULTI, we introduce cross-interaction terms between the beads belonging to the folded and disordered regions to generate conformation ensembles for full-length multidomain proteins such as hnRNP A1, TDP-43, G3BP1, hGHR-ECD, TIA1, HIV-1 Gag, polyubiquitin, and FUS. When back-mapped to all-atom resolution, SOP-MULTI trajectories faithfully recapitulate the scattering data over the range of the reciprocal space. We also show that individual folded domains preserve native contacts with respect to solved folded structures, and root-mean-square fluctuations of residues in folded domains match those obtained from all-atom molecular dynamics simulation trajectories of the same folded systems. SOP-MULTI force field is made available as a LAMMPS-compatible user package along with setup codes for generating the required files for any full-length protein with folded and disordered regions.
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Python 2.7.10 Language Reference
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Self-citation
- Authors
- Baratam, K., & Srivastava, A.
- Affiliations
- Indian Institute of Science Bangalore (IN)
- Corresponding author
- Srivastava, Anand
- Venue
- Journal of Chemical Theory and Computation
- Publisher
- American Chemical Society (ACS)
- Published
- 2024-11-05
- Volume
- 20
- Issue
- 22
- Pages
- 10179-10198
- ISSN
- 1549-9618 (ISSN-L)
- 1549-9626
- OpenAlex
- W4404074276
- Cited by
- 9
- References
- 117
- Citations by year
- 2026: 4 · 2025: 5
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Journal of Chemical Theory and Computation (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed (publishedVersion)
- NOT FOUND REPOSITORY (Indian Institute of Science Bangalore) (submittedVersion)
- Funders
- Indo-French Centre for the Promotion of Advanced Research (IFC/4132/RCF 2019/708)
- Wellcome Trust DBT India Alliance (IA/TSG/21/1/600245)
- Science and Engineering Research Board (MTR/2023/001040)
- Indian Institute of Science
- Department of Biotechnology, Ministry of Science and Technology, India (BT/PR40323/BTIS/137/78/2023)
- Department of Science and Technology, Ministry of Science and Technology, India
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- coarse-grained force field, multidomain proteins, intrinsically disordered proteins, conformational ensembles, flexible linkers, integrative structural biology, hnRNP A1, TDP-43, FUS, HIV-1 Gag, polyubiquitin, TIA-1, G3BP1
- MeSH terms
- Protein Domains, Polymers, Protein Conformation, Protein Folding, Molecular Dynamics Simulation, Intrinsically Disordered Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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