Simultaneous sampling of multiple transition channels using adaptive paths of collective variables

Area of Science:

• Computational chemistry
• Molecular dynamics
• Biophysics

Background:

• Understanding molecular transitions is crucial for biomolecular systems.
• Existing methods struggle with complex systems featuring multiple competing pathways.

Purpose of the Study:

• To introduce a novel molecular simulation method, multiPMD, for simultaneous identification of multiple transition pathways and their free-energy profiles.
• To enhance the analysis of complex molecular systems with competing or controversial transition routes.

Main Methods:

• The multiPMD method extends path-metadynamics (PMD) and multiple-walker PMD.
• It incorporates multiple paths and repulsive walkers for enhanced sampling.
• A "PathMap" visualization scheme is introduced to interpret free energy landscapes and path branching.

Main Results:

• Successfully identified two C7eq → C7ax transition paths in Ace-Ala-Nme.
• Mapped six PPII → PPII transition paths in Ace-(Pro)4-Nme.
• Demonstrated the ability of PathMap to visualize free energy ridges and transition channel dynamics.

Conclusions:

• MultiPMD offers a flexible and powerful approach for studying systems with multiple competing pathways.
• This method is particularly promising for analyzing complex biomolecular systems like proteins and nucleic acids.
• The PathMap visualization aids in understanding intricate molecular transition mechanisms.