  We examined protein residue networks (PRNs) from a local search perspective
to understand why PRNs are highly clustered when having short paths is
important for protein functionality. We found that by adopting a local search
perspective, this conflict between form and function is resolved as increased
clustering actually helps to reduce path length in PRNs. Further, the paths
found via our EDS local search algorithm are more congruent with the
characteristics of intra-protein communication. EDS identifies a subset of PRN
edges called short-cuts that are distinct, have high usage, impacts EDS path
length, diversity and stretch, and are dominated by short-range contacts. The
short-cuts form a network (SCN) that increases in size and transitivity as a
protein folds. The structure of a SCN supports its function and formation, and
the function of a SCN influences its formation. Several significant differences
in terms of SCN structure, function and formation is found between successful
and unsuccessful MD trajectories. By connecting the static and the dynamic
aspects of PRNs, the protein folding process becomes a problem of graph
formation with the purpose of forming suitable pathways within proteins.
