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Path-sampling strategies for simulating rare events in biomolecular systems
Lillian T Chong1, Ali S Saglam1, Daniel M Zuckerman2
1Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Current Opinion in Structural Biology
|December 17, 2016
Summary
Molecular dynamics simulations struggle with long timescales. Path sampling methods efficiently capture rare biomolecular transitions like protein folding and binding events.
Area of Science:
- Computational Biology
- Biophysics
- Biochemistry
Background:
- Molecular dynamics (MD) simulations have limitations in capturing long-timescale (milliseconds and beyond) biological processes.
- Conventional MD simulations (<10μs) often remain trapped in metastable states, failing to observe rare but crucial events like conformational changes or binding/unbinding.
Purpose of the Study:
- To highlight the limitations of conventional molecular dynamics simulations for studying rare events.
- To introduce and emphasize the utility of path sampling approaches for overcoming these limitations in biomolecular simulations.
Main Methods:
- Discusses the challenges of conventional molecular dynamics simulations in reaching biologically relevant timescales.
- Explains the principle of path sampling methods, which focus computational resources on transitions of interest.
Main Results:
- Conventional simulations are inefficient for observing rare events due to dwelling in metastable states.
- Path sampling approaches have been successfully applied for nearly two decades to study ms-timescale processes.
Conclusions:
- Path sampling methods are essential for generating pathways and calculating rate constants for rare biomolecular events.
- These methods enable the study of complex phenomena such as protein folding, large conformational changes, and protein (un)binding events.
