Protein folding mechanisms techniques

There is no doubt that the technique of chromatography (particularly affinity-based) will continue to make large advances as our understanding of the molecular mechanisms governing protein folding and enzyme-substrate interactions in-... 

The protein folding problem is of fundamental importance in modern structural biology. Recent advances in experimental techniques have helped to elucidate thermodynamic and kinetic mechanisms that underlie different stages of the folding process [1-6]. Computer simulations performed at various levels of molecular detail have played a central role in the interpretation of experimental studies. Molecular simulations using models based on fully atomic representations are becoming more accurate and more practical and are increasingly... 

NMR has become an indispensable analytical technique for studying rates of H D exchange at specific sites when a protein is deuterated. Such exchange rates provide information on secondary protein structure and are useful in investigating the mechanism of protein folding. 

This review will present an overview of current molecular mechanics techniques and discuss some of their limitations. We will then look at knowledge-based protein prediction strategies and examine the incorporation of such empirical rules into refinement methodologies for model protein systems. More comprehensive reviews of molecular dynamics simulations, knowledge-based protein modeling, and protein folding simulations are available. - " ... 

An interesting application of SDEL involved the folding mechanism of cytochrome The folding kinetics of cytochrome c has been studied extensively by a variety of experimental techniques. " The SDEL folding trajectories agree with several experimental observations including (1) the collapse of the protein without formation of secondary structures followed by formation of the terminal helices before the middle helix (see upper side of Figure 12),... 

As is usually the case in physical chemistry, theoretical studies inform experimental studies and vice versa. Many of the sophisticated experimental techniques in chemical kinetics to be discussed in Chapter 6 continue to yield details of the mechanism of protein folding. For example, the available data indicate that, in a number of proteins, a significant portion of the folding process occurs in less than 1 ms (10 s). Among the fastest events is the formation of helical and sheetlike structiu-es from a fully unfolded chain. Slower events include the formation of contacts between helical segments in a large protein. 

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