ABSTRACT
Functional characterization of a protein sequence is one of the most frequent problems
in biology. This task is usually facilitated by an accurate three-dimensional (3D) structure of the studied protein. A three-dimensional structure of natural proteins is guided by two distinct sets of principles operating on vastly different time scales: the laws of physics and the theory of evolution. Each of the two sets of principles that apply to the natural protein sequences gave rise to a class of protein structure prediction methods (Fig. 1) (Baker and Sali, 2001; Fiser et al., 2002).
