II. Geometrical framework for thinking about globular proteins: the power of poking

Abstract

Recently, we presented a framework for understanding protein structure based on the idea that simple constructs of holding hands or touching of objects can be used to rationalize the common characteristics of globular proteins. We developed a consistent approach for understanding the formation of the two key common building blocks of helices and sheets as well as the compatible assembly of secondary structures into the tertiary structure through the notion of poking pairwise interactions. Here we benchmark our predictions with a detailed analysis of structural data of over 4000 proteins from the Protein Data Bank. We also present the results of detailed computer simulations of a simplified model demonstrating a pre-sculpted free energy landscape, determined by geometry and symmetry, comprising numerous minima corresponding to putative native state structures. We explore the consequences of our model. Our results suggest that symmetry and geometry are a powerful guide to capture the simplicity underlying protein complexity. Statement for broader audienceA poking interaction in a chain causes two parts of a chain to poke towards each other. We use empirical data to establish a two-way link between geometry and chemistry through poking interactions and hydrogen bonds. We show that our simple and tractable geometrical model, superficially unrelated to proteins, can capture the essential features of a rich and incredibly complex protein molecule.