In silico protein design: fitting sequence onto structure.

In the last 10 yr, efforts have begun to combine the goals and approaches of computational molecular design and protein sequence analysis to provide tools for the rational mutagenesis and functional modification of proteins. These approaches use analysis of the three-dimensional structure of a protein to guide the selection of appropriate amino acid sequences to create desired properties or functions. The convergence of low-cost, high-speed computers, a tremendous increase in protein structure information, and a growing understanding of the forces that control protein structure has resulted in dramatic advances in the ability to control protein function and structure and to create the first truly artificial proteins. Various academic software packages have been developed for in silico protein design. The methods for selecting the protein structure, defining the portion to be designed, and choosing the input parameters for the software are described in this chapter.