Protein folding conformational unfolding model

Standard molecular mechanics (MM) force fields have been developed that provide a good description of protein structure and dynamics,21 but they cannot be used to model chemical reactions. Molecular dynamics simulations are very important in simulations of protein folding and unfolding,22 an area in which they complement experiments and aid in interpretation of experimental data.23 Molecular dynamics simulations are also important in drug design applications,24 and particularly in studies of protein conformational changes,25,26 simulations of the structure and function of ion channels and other membrane proteins,27-29 and in studies of biological macromolecular assemblies such as F-l-ATPase.30... 

The protein-folding problem is related to the determination of how and why a protein of a given amino acid sequence adopts a certain three-dimensional structure. A recent extension to the problem includes the question of how and why a protein adopts the misfolded or unfolded conformations. This article describes the different hierarchies of protein folding, the classical models and current... 

To check for the presence of an intermediate in a protein folding process, the temperatures at which the secondary structure (Tsec) and the tertiary structure (Ttert) of the folded conformation are half-formed can be compared. If both coincide, the protein loses the tertiary and the secondary structures simultaneously, and only a native conformation with secondary and tertiary structures ordered or an unfolded conformation with both structural levels unordered describe the process. If significant differences are observed in the crossing temperatures of concentration profiles, a new, intermediate third species with the secondary structure ordered and the tertiary unordered may be needed to explain the shift in the appearance of the tertiary and secondary structures. The difference of almost 20°C found between Tsec and Ttert in the above two experiments seems to guarantee the presence of an intermediate conformation in the folding of a-apolactalbumin, but only the multivariate resolution analysis of the suitable measurements (far-UV and near-UV CD spectra) together can confirm this hypothesis and model the appearance of the intermediate conformation. 

The results indicate that several of the FFs are competitive with the KBFF models for one of the systems, but none exhibited the overall balance between solute-solute, solute-solvent, and solvent-solvent distributions for aU the solutes as provided by the KBFF models. The NMA and water results are particularly concerning due to the central role of peptide-peptide interactions in determining the balance between folded and unfolded protein conformations. The observation that all the FFs display a significantly more positive solute-solute excess coordination number compared to... 

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