title: How special is the biochemical function of native proteins?
abstract: Native proteins perform an amazing variety of biochemical functions, including enzymatic catalysis, and can engage in protein-protein and protein-DNA interactions that are essential for life. A key question is how special are these functional properties of proteins. Are they extremely rare, or are they an intrinsic feature? Comparison to the properties of compact conformations of artificially generated compact protein structures selected for thermodynamic stability but not any type of function, the artificial (ART) protein library, demonstrates that a remarkable number of the properties of native-like proteins are recapitulated. These include the complete set of small molecule ligand-binding pockets and most protein-protein interfaces. ART structures are predicted to be capable of weakly binding metabolites and cover a significant fraction of metabolic pathways, with the most enriched pathways including ancient ones such as glycolysis. Native-like active sites are also found in ART proteins. A small fraction of ART proteins are predicted to have strong protein-protein and protein-DNA interactions. Overall, it appears that biochemical function is an intrinsic feature of proteins which nature has significantly optimized during evolution. These studies raise questions as to the relative roles of specificity and promiscuity in the biochemical function and control of cells that need investigation.
authors.affiliation: Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Skolnick
authors.affiliation: Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Mu
authors.initials: M
authors.lastname: Gao
authors.affiliation: Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhou
keywords: Enzymatic active sites; Protein structure; biochemical function; native proteins; protein conformation; protein interactions