Sequential vs. parallel protein-folding mechanisms: experimental tests for complex folding reactions

The recent emphasis on rough energy landscapes for protein folding reactions by theoreticians, and the many observations of complex folding kinetics by experimentalists provide a rationale for a brief literature survey of various empirical approaches for validating the underlying mechanisms. The determination of the folding mechanism is a key step in defining the energy surface on which the folding reactions occurs and in interpreting the effects of amino acid replacements on this reaction. Case studies that illustrate methods for differentiating between sequential and parallel channel folding mechanisms are presented. The ultimate goal of such efforts is to understand how the one-dimensional information contained in the amino acid sequence is rapidly and efficiently translated into three-dimensional structure.