The String Method with Swarms of Trajectories: A Tutorial for Free-Energy Calculations Along a Zero-Drift Pathway
The objective of this tutorial is to provide a comprehensive overview of the string method and its usage to determine a detailed transition pathway and the free-energy difference between two conformational states of a system. The computational protocol is illustrated in detail by setting out to calculate the free-energy difference between the C<sub>7eq</sub> and C<sub>7ax</sub> conformations of the short, terminally blocked peptide, <i>N</i>-acetyl-<i>N</i>'-methylalaninamide. Starting from a rectilinear transition pathway connecting the two conformations in the backbone-torsional subspace, an optimal zero-drift pathway (ZDP) is determined using the string method with a swarm of trajectories. The free-energy change along this path is then estimated using the path-collective variables (PCV) coordinate in the framework of the adaptive biasing force (ABF) importance-sampling algorithm.
Authors
- Chenyu Tang (ORCID: https://orcid.org/0000-0002-6914-7348)
- Haochuan Chen (ORCID: https://orcid.org/0000-0001-6447-1096)
- Christophe Chipot (ORCID: https://orcid.org/0000-0002-9122-1698)
- Emad Tajkhorshid (ORCID: https://orcid.org/0000-0001-8434-1010)
- Benoı̂t Roux (ORCID: https://orcid.org/0000-0002-5254-2712)
Institutions
- University of Illinois Urbana-Champaign (US)
- University of Chicago (US)
- Université de Lorraine (FR)
Publication Details
- Journal
- The Journal of Physical Chemistry B
- Published
- 2025-06-27
- DOI
- https://doi.org/10.1021/acs.jpcb.5c02470
- Citations
- 1
- Primary Topic
- Protein Structure and Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Université de Lorraine
- Conseil régional du Grand Est
- National Institute of General Medical Sciences
- Division of Molecular and Cellular Biosciences
- H2020 European Research Council