ABSTRACT
Here we present a model to estimate the interaction free energy contribution of each amino acid residue of a given protein. Protein interaction energy is described in terms of per-residue interaction factors, µ. Multibody interactions are implicitly captured in µ through the combination of amino acid terms (γ) guided by local conformation indices (σ). The model enables construction of an interaction factor heat map for a protein in a given fold, allows prima facie assessment of the degree of residue-residue interaction, and facilitates a qualitative and quantitative evaluation of protein association properties. The model was used to compute thermal stability of T4 bacteriophage lysozyme mutants across seven sites. Qualitative assessment of mutational effects provides a straightforward rationale regarding whether a particular site primarily perturbs native or non-native states, or both. The presented model was found to be in good agreement with experimental mutational data (R 2 = 0.73) and suggests an approach by which to convert structure space into energy space.
