Kinwalker

Kinwalker models cotranscriptional RNA folding trajectories at base-pair resolution to simulate kinetic folding processes and energy barrier–mediated structural transitions.

Key Features:

• Base-pair resolution modeling: Models folding trajectories at base-pair resolution to capture detailed structural transitions.
• Morgan-Higgs heuristic: Uses the Morgan-Higgs heuristic to connect local building blocks during trajectory construction.
• Barrier tree-based heuristic: Employs a barrier tree-based heuristic to navigate energy landscapes by considering barriers between structural states.
• Thermodynamic building blocks: Constructs secondary structures through stepwise combination of thermodynamically optimal building blocks corresponding to subsequences.
• Dynamic programming for block detection: Determines building blocks using standard dynamic programming techniques from RNA folding studies.
• Barrier-regulated transitions: Regulates each folding step by barrier heights between source and target structures.
• Initial-structure specification: Begins from a user-specified initial structure, defaulting to an open chain when unspecified.
• Minimum free energy progression: Progresses iteratively toward the minimum free energy structure during simulation.
• Sequence length support: Handles RNA sequences up to approximately 1500 nucleotides in length.
• Implementation: Implemented as part of the ViennaRNA Package.
• Validation: Validated against literature examples including bacteriophage cloverleaf structures, the adenine-sensing riboswitch, and the hok RNA with agreement to experimental evidence.

Scientific Applications:

• Cotranscriptional folding studies: Simulates cotranscriptional folding events and kinetic folding pathways of RNA sequences.
• Analysis of delayed folding: Investigates delayed folding phenomena exemplified by bacteriophage cloverleaf structures, the adenine-sensing riboswitch, and hok RNA.
• Comparison with experiments: Compares predicted folding trajectories with experimental evidence to assess folding kinetics and pathway plausibility.
• RNA dynamics and structural biology: Supports research on RNA dynamics and structural biology by providing kinetic folding predictions.

Methodology:

Constructs secondary structures by stepwise combination of thermodynamically optimal subsequence building blocks found by dynamic programming, models folding trajectories at base-pair resolution using the Morgan-Higgs and barrier tree-based heuristics, initiates from a user-specified initial structure (default open chain), and iteratively progresses toward the minimum free energy structure with transitions regulated by barrier heights between source and target structures.