Self-Organized Criticality in Proteins: Hydropathic Roughening Profiles of G-Protein Coupled Receptors

TL;DR

This paper demonstrates that hydropathic roughening profiles derived solely from amino acid sequences can reveal insights into the global and local chemical trends, functionality, and self-organized criticality of G-Protein Coupled Receptors (GPCRs).

Contribution

It introduces a sequence-based method to analyze protein properties and functionality without requiring structural data, highlighting self-organized criticality in proteins.

Findings

Hydropathic roughening profiles correlate with protein functionality.

Sequence-based analysis reveals chemical trends in GPCRs.

Profiles show self-organized criticality in protein structures.

Abstract

Proteins appear to be the most dramatic natural example of self-organized criticality (SOC), a concept that explains many otherwise apparently unlikely phenomena. Protein conformational functionality is often dominated by long-range hydro(phobic/philic) interactions which both drive protein compaction and mediate protein-protein interactions. Superfamily transmembrane GPCR are the largest family of proteins in the human genome; their amino acid sequences form the largest data base for protein-membrane interactions. While there are now structural data on the heptad transmembrane structures of representatives of several heptad families, here we show that fresh insights into global and some local chemical trends in GPCR properties can be obtained accurately from sequences alone, especially by separating the extracellular and cytoplasmic loops from transmembrane segments. The global mediation of long-range water-protein interactions occurs in conjunction with modulation of these interactions by roughened interfaces. Hydropathic roughening profiles are defined here solely in terms of amino acid sequences, and knowledge of protein coordinates is not required. Roughening profiles both for GPCR and some simpler protein families display accurate and transparent connections to protein functionality.