Protein Design Concepts

Protein chemistry has uncovered an apparently boundless variety and efficiency with which nature’s proteins perform their functions. They are a powerful incentive to attempt emulating nature’s marvels for our purposes. Alas, insofar as the terms ‘design’ and ‘engineering’ imply a rational, planned approach to the creation or modification of protein structure and function, both still remain beyond our capabilities. On the other hand, protein design, the construction of novel sequences without intentional similarity to existing ones, is a test-bed for our understanding. Designing a protein sequence from first principles may fail in an interesting way and expose previously unrecognized and faulty assumptions. In this article we will focus on current approaches in protein design and on the problems that have been encountered. In some specific situations, protein designers have been remarkably successful. But clear indications that show along which lines more effort must be invested are only slow to emerge.