Przewidywanie struktury białek: podejście boltzmannowskie i darwinowskie

Abstrakt

Efforts to solve the problem of protein folding have been traditionally rooted in two schools of thought named Boltzmannian' and Darwinian', after the scientists who defined the fundamental principles of statistical thermodynamics and evolutionary biology, respectively. One approach to protein structure prediction is based on the principles of physics, e.g. on the thermodynamic hypothesis, according to which the native structure of a protein corresponds to the global minimum of its free energy under given conditions. Accordingly, the physics-based methods model the process of protein folding by simulating the conformational changes and searching for the free energy minimum. The other approach is based on the principles of evolution, in particular the empirical rule that evolutionarily related (homologous) proteins usually retain the same three-dimen-sional fold despite the accumulation of divergent mutations. Evolution-based methods attempt to map the sequence of the target protein to the structure of another protein (a template), model the overall fold of the target based on that of the template and infer how the target structures will change due to substitutions, insertions and deletions, as compared with the template. This review summarizes the basics of protein structure prediction by both types of approaches and discusses the issue of model quality evaluation.