Progress and Challenges in Computational Protein Design

Ban YA, Röthlisberger-Grabs D, Althoff EA, and Zanghellini A. Protein Engineering Handbook, Volume 3, 2012: 363-406

Abstract: The tremendous increase in the amount of protein structural information acquired during the past four decades has opened new avenues – first and foremost for the detailed understanding of protein function at the molecular level. The rational, structure-based engineering of proteins–as opposed to purely stochastic and experimental methods such as directed evolution–is now a possibility for a wide variety of proteins and enzymes of scientific and industrial interest. Among the techniques employed for rational protein engineering, computational protein design (CPD) is a relatively recent approach aimed at combining physical chemistry models governing amino acids and protein structure with advanced computational algorithms to automate the task of redesigning protein sequences, to alter their structure, and to impart them with new function(s). The first part of this chapter includes a detailed summary of the key concepts behind computational protein design, and summarizes the “state-of-the-art” software packages and techniques that can be used practically. In the subsequent four sections those areas of protein engineering where computational protein design has been successful in the recent past will be reviewed, together with details of the present challenges and anticipated future developments in the application of this technique.