Modeling Protein Folding: the Beauty and Power of Simplicity

It is argued that simplified models capture key features of protein stability and folding, whereas more detailed models may be more appropriate for protein structure prediction. A brief overview of experimental and theoretical results is presented that corroborates these points. I argue that statistical models capture the key principle of protein stability-cooperativity- and therefore provide a reasonable estimate of protein free energy whereas more detailed but less physically transparent calculations fail to do so. I also explain that the previously published claim that simple models give predictions that are inconsistent with experiments on polypeptide block-copolymers is based on incomplete analysis of such experiment.