Li, Lunna;
Casalini, Tommaso;
Arosio, Paolo;
Salvalaglio, Matteo;
(2021)
Modelling the structure and interactions of intrinsically disordered peptides with multiple-replica, metadynamics-based sampling methods and force-field combinations.
ChemRxiv: Cambridge, UK.
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Abstract
Intrinsically disordered proteins (IDPs) play a key role in many biological processes, including the formation of biomolecular condensates within cells. A detailed characterization of their configurational ensemble and structure-function paradigm is crucial for understanding their biological activity and for exploiting them as building blocks in material sciences. In this work, we incorporate bias-exchange metadynamics and parallel-tempering well-tempered metadynamics with CHARMM36m and CHARMM22* to explore the structural and thermodynamic characteristics of a short archetypal disordered sequence derived from a DEAD-box protein. The conformational landscapes emerging from our simulations are largely congruent across methods and forcefields. Nevertheless, differences in fine details emerge from varying forcefield/sampling method combinations. For this protein, our analysis identifies features that help to explain the low propensity of this sequence to undergo self-association in vitro, which can be common to all force-field/sampling method combinations. Overall, our work demonstrates the importance of using multiple force-field/enhanced sampling method combinations for accurate structural and thermodynamic information in the study of general disordered proteins.
| Type: | Working / discussion paper |
|---|---|
| Title: | Modelling the structure and interactions of intrinsically disordered peptides with multiple-replica, metadynamics-based sampling methods and force-field combinations |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.26434/chemrxiv-2021-4gg4g |
| Publisher version: | https://doi.org/10.26434/chemrxiv-2021-4gg4g-v2 |
| Language: | English |
| Additional information: | The content is available under CC BY 4.0 License (http://creativecommons.org/licenses/by/4.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Chemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10168187 |
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