Why aren't the small worlds of protein contact networks smaller

TL;DR

This study investigates why protein contact networks do not have shorter average shortest path lengths despite their importance, revealing that optimizing long-range interactions can improve search performance and challenge existing assumptions about network topology.

Contribution

The paper demonstrates that emphasizing short-range links in protein contact networks enhances search efficiency and shows that reducing long-range links does not necessarily improve network performance.

Findings

Shorter average path lengths do not guarantee easier global optimization.

Prioritizing short-range interactions improves search performance.

Randomizing long-range links does not outperform natural protein contact networks.

Abstract

Computer experiments are performed to investigate why protein contact networks (networks induced by spatial contacts between amino acid residues of a protein) do not have shorter average shortest path lengths in spite of their importance to protein folding. We find that shorter average inter-nodal distances is no guarantee of finding a global optimum more easily. Results from the experiments also led to observations which parallel an existing view that neither short-range nor long-range interactions dominate the protein folding process. Nonetheless, runs where there was a slight delay in the use of long-range interactions yielded the best search performance. We incorporate this finding into the optimization function by giving more weight to short-range links. This produced results showing that randomizing long-range links does not yield better search performance than protein contact networks au natural even though randomizing long-range links significantly reduces average path lengths and retains much of the clustering and positive degree-degree correlation inherent in protein contact networks. Hence there can be explanations, other than the excluded volume argument, beneath the topological limits of protein contact networks.