Toward the rational design of mechanical proteins

The biological functions of proteins have long been studied in a manner that has deprived us of a basic mode of inquiry: physical manipulation. In recent years theoretical and technological advances have made possible tools to directly manipulate single molecules mechanically. The atomic force microscope is a flexible and robust platform that allows us this ability. At the same time computational tools have become increasingly common companions and facilitators of theoretical and experimental science. Of the many mechanically important proteins titin and titin-like proteins are important on many levels. From a physiological understanding of the way mechanical strength is propagated from sarcomere to muscle tissue, to a theoretical understanding of the molecular mechanisms contributing to the mechanical design of proteins in general. We have used a combination of computational techniques on a basis of experimental evidence to make predictions and then test them experimentally to ultimately grow our body of knowledge concerning the mechanical design of proteins.