Physical Origins of Protein Superfamilies

Abstract

In this work, we discovered a fundamental connection between selection for protein stability and emergence of preferred structures of proteins. Using standard exact 3-dimensional lattice model we evolve sequences starting from random ones and determining exact native structure after each mutation. Acceptance of mutations is biased to select for stable proteins. We found that certain structures, "wonderfolds", are independently discovered numerous times as native states of stable proteins in many unrelated runs of selection. Diversity of sequences that fold into wonderfold structures gives rise to superfamilies, i.e. sets of dissimilar sequences that fold into the same or very similar structures. Wonderfolds appear to be the most designable structures out of complete set of compact lattice proteins. Furthermore, proteins having wondefolds as their native structure tend to be most thermostable among all evolved proteins. This effect is purely due to the favorable geometric properties of wonderfolds and, thus, dominates any dependence on sequences. The present work establishes a model of prebiotic structure selection, which identifies dominant structural patterns emerging upon optimization of proteins for survival in hot environment. Convergently discovered prebiotic initial superfamilies with ''wonderfold'' structures could have served as a seed for subsequent biological evolution involving gene duplications and divergence.3

The network of sequence flow between protein structures

“…The graph clearly shows the existence of structures that attract sequences from many other folds. The potential existence of sinks was noted in the past based on 3 ϫ 3 ϫ 3 lattice simulations (6,33). All of the top attractors are in the largest component.…”

Protein Products of Tandem Gene Duplication: A Structural View

“…It would be possible to tune such a model to recapitulate known evolutionary events; this would provide a tool to evaluate the probability of an evolutionary relationship between two proteins, not unlike the work of Shaknovich and colleagues at the residue level using simple lattice models (Dokholyan et al, 2003;Zeldovich et al, 2006).…”

A Dynamic Model for the Evolution of Protein Structure

“…Yet another approach, found in a study by [8], attempts to reconstruct protein evolutionary history via simulation. [8] demonstrates that, given stability as the selection mechanism in each iteration, random protein sequences often converge on proteins with specific structures, so called "wonderfolds."…”

“…[8] demonstrates that, given stability as the selection mechanism in each iteration, random protein sequences often converge on proteins with specific structures, so called "wonderfolds." The authors consider these emergent thermostable wonderfolds as potential pre-biotic precursors to the biotic protein structure hierarchy, ones that likely arose in a hot environment and needed their thermostability.…”