Simplified Models of Protein Folding

Abstract

Protein folding is one of the most basic physico-chemical self-assembly processes in biology. Elucidation of its underlying physical principles requires modeling efforts at multiple levels of complexity [1]. As in all theoretical endeavors, the degree of simplification in modeling protein behavior depends on the questions to be addressed. The motivations for using simplified models to study protein folding are at once practical and intellectual. Realistically, a truly ab initio solution to the Schrödinger equation for a protein and its surrounding solvent molecules is currently out of the question. Although classical (Newtonian) descriptions based on geometrically high-resolution all-atom molecular dynamics have provided much useful insight, these models are computationally costly. Moreover, it is unclear whether common empirical potential functions used in such all-atom approaches are ultimately adequate. In this context, simplified models offer a complementary and efficient means for posing questions and testing hypotheses. Similar in spirit to the Ising model of ferromagnetism, simplified models of protein folding are designed to capture essential physics, and are geared towards the discovery of higher organizing principles [2] while omitting details deemed unimportant for the question at hand.