Biomolecular conformational transitions are essential to biological functions. Most experimental methods report on the long-lived functional states of biomolecules, but information about the transition pathways between these stable states is generally scarce. Such transitions involve short-lived conformational states that are difficult to detect experimentally. For this reason, computational methods are needed to produce plausible hypothetical transition pathways that can then be probed experimentally. Here we propose a simple and computationally efficient method, called ANMPathway, for constructing a physically reasonable pathway between two endpoints of a conformational transition. We adopt a coarse-grained representation of the protein and construct a two-state potential by combining two elastic network models (ENMs) representative of the experimental structures resolved for the endpoints.
ANMPathway determines the most probable (lowest energy) transition pathway between two stable endpoints of a conformational transition. Conceptually, ANMPathway represents a direct application of the string method to a two-state CG system approximated by ANM energy surfaces. The result is a sequence of PDB structure (a “string”) smoothly linking the two endpoints.
- Generates a continuous minimum energy pathway from two End-Point PDB structures containing the same number and order of residues.
- ANMPathway sends the calculated pathway by email. Typical jobs take several minutes to an hour (maximum 12 hours). The result also contains a movie of the structural transition along the calculated pathway and a list of non-native contacts formed during the transition.
- NAMD scripts for converting the CG pathway to an all-atom pathway is coming soon.
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