结构生物学sturcture biology explore-57.pdfVIP

447 Knowledge-based potential functions in protein design William P Russ and Rama Ranganathan* Predicting protein sequences that fold into specific native sequence space and refining the scoring functions. In this three-dimensional structures is a problem of great potential review, we examine the ways in which knowledge-based complexity. Although the complete solution is ultimately potentials have been used to influence protein design and rooted in understanding the physical chemistry underlying suggest that further study of the mechanistic origin of the complex interactions between amino acid residues that these potentials may lead to a better understanding of the determine protein stability, recent work shows that empirical physical chemistry of proteins. information about these first principles is embedded in the statistics of protein sequence and structure databases. This Sources of imprecision and complexity in review focuses on the use of ‘knowledge-based’ potentials protein design derived from these databases in designing proteins. In The core problem of rational protein design is the con- addition, the data suggest how the study of these empirical struction of a potential function that describes protein potentials might impact our fundamental understanding of stability. The logical basis for this energy function arises the energetic principles of protein structure. from the thermodynamic hypothesis that the native structure of a protein is given