The folding of disulfide-rich proteins.

The articles in this forum issue describe various aspects of the folding of disulfide-rich proteins. They include review articles using proteins such as bovine pancreatic trypsin inhibitor as models to highlight the range of folding pathways seen in disulfide-rich proteins, along with a detailed analysis of the methods used to study them. Following two comprehensive reviews on the methods and applications of protein folding, three original articles in this issue focus on two specific classes of disulfide-rich proteins that have applications in drug design and development, namely cyclotides and conotoxins. Cyclotides are head-to-tail cyclic and disulfide-rich proteins from plants and function as a defense against insect attack. Conotoxins are the disulfide-rich components of the venom of marine cone snails that is used to capture prey. These research articles report on factors that modulate protein folding pathways in these molecules and determine the outcomes of protein folding, that is, yield and heterogeneity of products. Finally, the issue concludes with a comprehensive review on a different type of disulfide bond, namely those that have a functional rather than structural role in proteins, with a particular focus on allosteric disulfide bonds that modify protein function.