Solution to the Protein Folding Problem
This chapter unravels a first-principle solution to the protein folding problem. The solution incorporates the dynamic interplay between the formation of packing defects and the interfacial tension created by such defects. Thus, the solution symbiotically combines a structural and epistructural approach to compute the dynamic entanglement between protein chain and solvent. The structural perspective explores the concept of wrapping, its intimate relation to cooperativity and its bearing on the expediency and reproducibility of the folding process. Wrapping refers to the environmental enhancement of intramolecular electrostatic interactions through an exclusion of surrounding water that takes place as the chain folds onto itself. In this way a many-body picture of the folding process emerges whereby the folding chain interacts with itself and at the same time shapes the microenvironments that stabilize or destabilize the intramolecular interactions. This picture reflects a dynamic competition between chain folding and backbone hydration, where ultimately, backbone hydrogen bonds prevail through cooperative wrapping, upholding the picture that “folding is a struggle for the survival of backbone hydrogen bonds”.
KeywordsFolding Process Interfacial Free Energy Folding Pathway Backbone Hydrogen Bond Folding Dynamic