Protein folding thermodynamics and dynamics: Where physics, chemistry, and biology meet

The protein folding has made a full circle, as attention is again focused on specific proteins and details of their folding mechanism. However, these questions are asked at a new level of sophistication of both theory and experiment. Understanding of general principles of folding and vastly improved computer power make it possible to develop tractable models that sometimes achieve an atomic level of accuracy. Further, a better general understanding of the requirements for polypeptide sequences to fold led to establishment of direct links between protein folding and evolution of their sequences. This review summarizes basic questions and presents simple, coarse-grained models that provide a basis for a fundamental understanding of protein folding thermodynamics and kinetics. It also discusses more recent developments (over the last five years) that focus on detailed studies of folding mechanisms of specific proteins.