title: Free energy diagrams for protein function.
abstract: Simplified representations can be powerful. Two common examples are sequence logos and ribbon diagrams. Both have been extraordinarily successful in capturing complex static features of sequences and structures. Capturing function is challenging, since activation involves triggered dynamic shifts between ON and OFF states. Here, we show that simple funnel drawings can capture and usefully portray proteins by their cellular triggering mechanism. The funnel shape around the proteins' native states can describe mechanisms of upstream signal integration and downstream response. "Function diagrams" are important: they can combine diverse biochemical data to visually distinguish among activation (or recruitment) mechanisms and tag proteins in cellular networks, clarifying their mechanism at a glance. We create templates for function classification and suggest that they can extend signaling pathway maps. Of note, the diagrams describe free energy landscapes; thus, they can be quantified. We name our dynamic free-energy diagrams dFEDs.
authors: Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; Sackler Institute of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: nussinor@helix.nih.gov.
authors: Ruth
authors: R
authors: Nussinov
authors: Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
authors: Chung-Jung
authors: CJ
authors: Tsai
mesh_terms: D011487:Protein Conformation; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013816:Thermodynamics
chemical_list: D011506:Proteins