Time-Dependent Markov State Models for Single Molecule Force Spectroscopy.

Area of Science:

• Computational Chemistry
• Molecular Dynamics
• Statistical Mechanics

Background:

• Analyzing molecular behavior under mechanical stress is crucial for understanding material properties.
• Traditional methods may struggle to capture dynamic changes during stretching experiments.

Purpose of the Study:

• To introduce a novel approach using time-dependent Markov state models (TD-MSMs) for molecular-scale analysis of stretching experiments.
• To demonstrate the ability to derive molecular insights from force-extension curves.

Main Methods:

• Construction of a master Markov state model (MSM) at a reference extension.
• Generation of time-dependent Markov state models (TD-MSMs) from the master-MSM for specific stretching conditions.
• Development and application of state-specific force models.
• Calculation of force-extension behavior across various ensembles.
• Quantification of network topology changes using mechanical disposition.

Main Results:

• A single master-MSM can generate all required TD-MSMs for diverse stretching scenarios.
• State-specific force models enable accurate calculation of force-extension curves.
• The concept of mechanical disposition effectively relates changes in network topology to applied forces.
• Successful proof-of-principle demonstrated on a stretched alanine decapeptide under time-varying force.

Conclusions:

• TD-MSMs offer a powerful framework for obtaining molecular-scale insights into mechanical stretching.
• This method simplifies the generation of dynamic models for various experimental conditions.
• The approach provides a quantitative link between molecular structure changes and macroscopic mechanical response.