Abstract
Current protein classification methods treat high-resolution structures as static entities. However, experiments have well documented the dynamic nature of proteins. With knowledge that thermodynamic fluctuations around the high-resolution structure contribute to a more physically accurate and biologically meaningful picture of a protein, the concept of a protein's energetic profile is introduced. It is demonstrated on a large scale that energetic profiles are both diagnostic of a protein fold and evolutionarily relevant. Development of Structural Thermodynamic Ensemble-based Protein Homology (STEPH), an algorithm that searches for local similarities between energetic profiles, constitutes a first step towards a long-term goal of our laboratory to integrate thermodynamic information into protein-fold classification approaches.