Quantitative Molecular Scaling Theory of Protein Amino Acid Sequences, Structure, and Functionality

Abstract

Here we review the development of protein scaling theory, starting from backgrounds in mathematics and statistical mechanics, and leading to biomedical applications. Evolution has organized each protein family in different ways, but scaling theory is both simple and effective in providing readily transferable dynamical insights complementary for many proteins represented in the 90 thousand static structures contained in the online Protein Data Base (PDB). Scaling theory is a simplifying magic wand that enables one to search the hundreds of millions of protein articles in the Web of Science, and identify those proteins that present new cost-effective methods for early detection and/or treatment of disease through individual protein sequences (personalized medicine). Critical point theory is general, and recently it has proved to be the most effective way of describing protein networks that have evolved towards nearly perfect functionality in given environments (self-organized criticality). Evolutionary patterns are governed by common scaling principles, which can be quantified using scales that have been developed bioinformatically by studying thousands of PDB structures. The most effective scales involve either hydropathic globular sculpting interactions averaged over length scales centered on membrane dimensions, or exposed beta strand propensities associated with aggregative (strong) protein-protein interactions.