Evolving Conformation Paths to Model Protein Structural Transitions

Proteins are dynamic biomolecules. A structure-by-structure characterization of a protein's transition between two different functional structures is central to elucidating the role of dynamics in modulating protein function and designing therapeutic drugs. Characterizing transitions challenges both dry and wet laboratories. Some computational methods compute discrete representations of the energy landscape that organizes structures of a protein by their potential energies. The representations support queries for paths (series of structures) connecting start and goal structures of interest. Here we address the problem of modeling protein structural transitions under the umbrella of stochastic optimization and propose a novel evolutionary algorithm (EA). The EA evolves paths without reconstructing the energy landscape, addressing two competing optimization objectives, energetic cost and structural resolution. Rather than seek one path, the EA yields an ensemble of paths to represent a transition. Preliminary applications suggest the EA is effective while operating under a reasonable computational budget.