Wrapping Patterns Along Folding Trajectories

To take into account the effect of wrapping on dielectric-dependent pairwise interactions and assess its role in defining cooperativity, we have adopted a semiem-pirical procedure to algorithmically keep track of the conformation-dependent microenvironments. Thus, the in-bulk potential energy contributions are regarded as zero-order terms, while cooperative effects arise due to the wrapping of favorable interactions brought about by hydrophobic third-body participation (cf. Fig. 3.2c). 

A basic question is addressed through this analysis What is the dynamic relevance of optimal wrapping in regard to the protein s commitment to fold To tackle this question, we analyze a representative simulation for the thermophilic variant of protein G. This simulation performed at 313 K, pFI 7, consists of 106 steps and was essentially reproduced in 66 of 91 FM runs. All the runs generated a stationary fold within RMSD 4 A from the native structure (PDB entry 1GB44) and a dramatic decrease in potential energy around 0.6 ms (Fig. 3.3). 

The wrapping results from Figs. 3.4 and 3.6 are more specific and informative than earlier attempts at establishing whether buried surface area is commensurate with hydrogen bond formation [13, 32], It is difficult to infer from such studies whether hydrophobic collapse triggers hydrogen bond formation or whether the latter directs the former. However, Figs. 3.4 and 3.6 reveal that the productive 

This approximate law holds for both native structure [22] and folding dynamics [2], In this regard, this wrapping motif may be regarded as a structural element that captures the basic component of energy transduction from hydrophobic association to structure formation. Furthermore, it implies that a fundamental constraint in protein architecture applicable to native structures applies also throughout the folding trajectory. 

5 Nanoscale Solvation Theory of Folding Cooperativity Dynamic Benchmarks and Constant of Motion 

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