Knowledge-based potentials in protein design

Curr Opin Struct Biol. 2006 Aug;16(4):508-13. doi: 10.1016/ Epub 2006 Jul 14.


Knowledge-based potentials are statistical parameters derived from databases of known protein properties that empirically capture aspects of the physical chemistry of protein structure and function. These potentials play a key role in protein design by improving the accuracy of physics-based models of interatomic interactions and enhancing the computational efficiency of the design process by limiting the complexity of searching sequence space. Recently, knowledge-based potentials (in isolation or in combination with physics-based potentials) have been applied to the modification of existing protein function, the redesign of natural protein folds and the complete design of a non-natural protein fold. In addition, knowledge-based potentials appear to be providing important information about the global topology of amino acid interactions in natural proteins. A detailed study of the methods and products of these protein design efforts promises to greatly expand our understanding of proteins and the evolutionary process that created them.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Databases, Protein
  • Protein Engineering*
  • Proteins / chemistry*
  • Proteins / genetics*
  • Proteins / physiology*


  • Proteins