Protein frustratometer: a tool to localize energetic frustration in protein molecules

Abstract

The frustratometer is an energy landscape theory-inspired algorithm that aims at quantifying the location of frustration manifested in protein molecules. Frustration is a useful concept for gaining insight to the proteins biological behavior by analyzing how the energy is distributed in protein structures and how mutations or conformational changes shift the energetics. Sites of high local frustration often indicate biologically important regions involved in binding or allostery. In contrast, minimally frustrated linkages comprise a stable folding core of the molecule that is conserved in conformational changes. Here, we describe the implementation of these ideas in a webserver freely available at the National EMBNet node-Argentina, at URL: http://lfp.qb.fcen.uba.ar/embnet/.

Figure 1.

Frustratometer server output. An example of the localized frustration and minimally frustrated networks in protein structures (pdb: 2FCK) Left: the protein backbone is displayed as blue ribbons, the direct inter-residue interactions with solid lines and the water-mediated interactions with dashed lines. Minimally frustrated interactions are shown in green, highly frustrated contacts in red, neutral contacts are not drawn. Right: Projection of local frustration distribution in amino acid sequence. The number of contacts within 5A of the C-alpha of each residue is plotted, as classified according to their frustration index.