A one-way shooting algorithm for transition path sampling of asymmetric barriers

Area of Science:

• Computational chemistry
• Biomolecular simulations
• Statistical mechanics

Background:

• Activated processes in biomolecules often feature complex, asymmetric free energy barriers.
• Efficiently sampling these transition paths is crucial for understanding molecular mechanisms.
• Existing methods like aimless shooting have limitations in certain dynamic regimes.

Purpose of the Study:

• To introduce a novel transition path sampling shooting algorithm.
• To enhance the efficiency of sampling activated processes with asymmetric free energy barriers.
• To adapt existing shooting methods for improved performance in diffusive systems.

Main Methods:

• Development of a fictitious potential to bias shooting points towards the transition state.
• Integration of this biased approach with the one-way shooting technique.
• Application to a 2D Langevin model, peptide association, and protein dimer dissociation.

Main Results:

• Demonstrated significant increases in sampling efficiency across all test systems.
• Validated the algorithm's effectiveness on diverse models, including biomolecular examples.
• Showcased the advantage of the biased shooting point in overcoming sampling challenges.

Conclusions:

• The novel algorithm provides a more efficient route for exploring complex activated processes.
• This method is particularly beneficial for systems with asymmetric free energy landscapes.
• The approach offers a valuable tool for advancing molecular dynamics simulations.