Protein folding continuous models

To solve the greatest questions of protein folding, however, this gap must be bridged. Obviously, predicted folding pathways and mechanisms axe only meaningful if the physical significance of the model can be established as well. This is also true for the continued development and/or refinement of simplified models for reliable structure predictions. In... 

Typically, the in vitro folding of a single domain globular protein resembles a first-order phase transition in the sense that the thermodynamic properties undergo an abrupt change, and the population of intermediates at equilibrium is very low. In other words, the process is cooperative and is well described by a two-state model [8]. The first attempts to explain protein folding cooperativity focused on the formation of secondary structure. Theoretical and experimental analysis of coil-helix transitions indeed proved that the process is cooperative [167]. However, the helix-coil transition is always continuous [168], and thus it cannot explain the two-state behavior of the protein folding transition. 

But in terms of these fundamentals, we would dare to say that an important progress had been achieved over the last several years. Previously, at the time of Anfinsen, protein folding seemed a fundamental physics mystery. People could not imagine how it could be happening even in principle. Now, there is at least an overall understanding of the basic physics behind folding, as we tried to outline in the present chapter. There are lattice models, which are very much unlike proteins in many respects (too many and too obvious to list) — but which are like proteins in two most important aspects they have the same fundamental difficulties, such as Levinthal paradox, and they do fold. And we understand this model pretty well But, of course, the study continues in many directions... 

Abstract. Despite its apparent simplicity the Ramachandran map has been an enormously successful tool for describing and understanding protein structure. Thirty-five years after its invention, it is still used daily for checking the quality of experimental and modeled protein structures. It is, moreover, founded on a rational, reduced-coordinate model of the polypeptide chain which continues to be useful in computational attempts at predicting protein folding. 

Fully atomistic simulations are the most realistic of the three simulation methods. They include a fully detailed description of the amino acids comprising the protein, and they are thus much more true to life than the other models. In addition, solvent molecules may be added explicitly or implicitly to the simulation. Because of this extreme detail, a simulation of a small protein may require the treatment of thousands of atoms. Fully atomic simulations are thus extremely computationally expensive, and only short time scales can be explored. As computational power continues to increase, so do the time scales accessible with this method. Nevertheless, fully atomic simulations still cannot capture kinetic information they are, however, useful in understanding important local interactions that drive protein folding. 

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