The FoldX web server: an online force field

Abstract

FoldX is an empirical force field that was developed for the rapid evaluation of the effect of mutations on the stability, folding and dynamics of proteins and nucleic acids. The core functionality of FoldX, namely the calculation of the free energy of a macromolecule based on its high-resolution 3D structure, is now publicly available through a web server at http://foldx.embl.de/. The current release allows the calculation of the stability of a protein, calculation of the positions of the protons and the prediction of water bridges, prediction of metal binding sites and the analysis of the free energy of complex formation. Alanine scanning, the systematic truncation of side chains to alanine, is also included. In addition, some reporting functions have been added, and it is now possible to print both the atomic interaction networks that constitute the protein, print the structural and energetic details of the interactions per atom or per residue, as well as generate a general quality report of the pdb structure. This core functionality will be further extended as more FoldX applications are developed.

Figure 1

How to set up a calculation in the FoldX web server. After selecting the pdb files by browsing the local pc or by entering the pdb identifier for download from the database, the user selects the calculations through tick boxes. After setting some optional parameters, the web server displays the results for download.

Figure 2

A typical result of the FoldX web server: a stability analysis of an SH3 domain (1shg). (A) The free energy of folding (the stability) of the protein broken down into the energy components used by FoldX is shown. (B) The contribution of each residue to the stability of the protein and (C) a pdb file colour coded according to the data in (B)—blue indicates highly stable regions and red indicates instable regions.