Physics and Biology of Protein Folding


Nobuhiro Go


Protein molecules fold spontaneously into the native conformations specific to their amino acid sequence under the physiological conditions in the living cell. Only in the native state, protein molecules carry out their biological function. This flow of logic, i.e., from information (amino acid sequence) to structure (native conformation) and from structure to function, is one of the most important concepts in biology. The process of protein folding is the mechanism of decoding the information about the three-dimensional structure in the native state encoded in the amino acid sequence. In the biological perspective, protein folding has been studied for years with the eventual goal of find a path from sequence to structure. Many organized efforts have been made along this line in Japan.


Even though protein folding is a very important and difficult biological problem, it is at the same time a very interesting problem for physics. In the physical perspective, protein folding is analogous to phase transition. The main problem there is to elucidate the essential point of protein's extraordinary ability to self-organize into their specific native three-dimensional structures. Nearly thirty years ago I started a theoretical study of protein folding from the point of view of statistical mechanics. A main theoretical tool I employed was simulation of conformational dynamics of simplified lattice models of protein, which, after twenty years, became very popular among theoretical biophysicists. As a result of these studies, I proposed a concept of Consistency Principle (several years later also proposed by Peter Wolynes under the name of Principle of Minimum Frustration) as a basic characteristic of protein molecules for their ability to self-assemble to their native three-dimensional structures. The logic here is that protein molecules satisfy the consistency principle, and the ability to self-assemble can be deduced from the consistency principle. The later part of the logic is that of physics. Then, the problem remains, i.e., why is the consistency principle satisfied by protein molecules? The answer is that only such molecules that satisfy the principle have been selected during evolution and are now being used as protein molecules. Thus, the very interesting physics of protein molecules has its origin in the biological evolution.



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