Li, Lunna;
Casalini, Tommaso;
Arosio, Paolo;
Salvalaglio, Matteo;
(2022)
Modeling the Structure and Interactions of Intrinsically Disordered Peptides with Multiple Replica, Metadynamics-Based Sampling Methods and Force-Field Combinations.
Journal of Chemical Theory and Computation
, 18
(3)
pp. 1915-1928.
10.1021/acs.jctc.1c00889.
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Abstract
Intrinsically disordered proteins 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 force fields. Nevertheless, differences in fine details emerge from varying combinations of force-fields and sampling methods. For this protein, our analysis identifies features that help to explain the low propensity of this sequence to undergo self-association in vitro, which are common to all force-field/sampling method combinations. Overall, our work demonstrates the importance of using multiple force-field and sampling method combinations for accurate structural and thermodynamic information in the study of disordered proteins.
| Type: | Article |
|---|---|
| Title: | Modeling the Structure and Interactions of Intrinsically Disordered Peptides with Multiple Replica, Metadynamics-Based Sampling Methods and Force-Field Combinations |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acs.jctc.1c00889 |
| Publisher version: | https://doi.org/10.1021/acs.jctc.1c00889 |
| Language: | English |
| Additional information: | This is an Open Access article published under a Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Cluster chemistry, Computer simulations, Molecular mechanics, Peptides and proteins, Potential energy |
| UCL classification: | 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 UCL > Provost and Vice Provost Offices > UCL BEAMS UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10144686 |
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