Quantifying Inter-Residue Contacts through Interaction Energies

The validity and accuracy of protein modeling is dependent
on constructing
models that account for the inter-residue interactions crucial for
protein structure and function. Residue interaction networks derived
from interatomic van der Waals contacts have previously demonstrated
usefulness toward designing protein models, but there has not yet
been evidence of a connection between network-predicted interaction
strength and quantitative interaction energies. This work evaluates
the intraprotein contact networks of five proteins against ab initio
interaction energies computed using symmetry-adapted perturbation
theory. To more appropriately capture the local chemistry of the protein,
we deviate from traditional protein network analysis to redefine the
interacting nodes in terms of main chain and side chain functional
groups rather than complete amino acids. While there is no simple
correspondence between the features of the contact network and actual
interaction strength, random forest models constructed from minimal
structural, network, and chemical descriptors are capable of accurately
predicting interaction energy. The results of this work serve as a
foundation for the development and improvement of functional group-based
contact networks.