DrDiff

DrDiff analyzes kinetics and thermodynamics of two-state biomolecular folding trajectories using stochastic drift-diffusion theory to characterize free-energy profiles, transition times, and coordinate-dependent drift and diffusion coefficients.

Key Features:

• Thermodynamic Profiling: Determines the coordinate-dependent free-energy profile F(Q) for characterizing molecular stability and folding pathways.
• Kinetic Analysis: Calculates folding time (τ_f) and transition path time (τ_TP) from trajectory data to quantify temporal aspects of transitions.
• Drift and Diffusion Coefficients: Extracts drift velocity v(Q) and diffusion coefficient D(Q) from time traces for coordinate-dependent dynamical modelling.
• Transition Path Analysis: Analyzes transition paths and first-passage times to characterize rare transition-state events.

Scientific Applications:

• Prion protein (PrP) folding: Analyzes folding/unfolding simulations of PrP using a coarse-grained Cα-level Go-model and reproduces a double-well free-energy profile F(Q), the "X" shape of τ_f(T), and a linear τ_TP(T) dependence.
• Rare-event processes: Characterizes kinetic and thermodynamic properties in systems where rare transition-state events are critical, such as prion misfolding and aggregation.

Methodology:

DrDiff employs numerical integration of the Langevin equation to recover input coefficients, validates results against known diffusion models, and enables comparison with Bayesian analysis and the fep1D algorithm.