The inherent symmetry or higher order correlations in protein structures are also relevant in the context of energy landscape theory, as it was predicted that funnelled landscapes and low energy structures are easier to be realized when symmetry prevails [56]. Since IDPs are not at learn more all fundamentally different (based on basic physical chemistry) to their folded counterparts similar principles will be valid in their case, too. It is thus suggested to exploit the fundamental building principles of protein structures for the generation of reliable and meaningful structural ensembles of IDPs by finding and using adequate sequence alignment

techniques to identify structural homologues and existing basic motifs. The proposed strategy will rely on a pre-generated large pool of structures from which most suitable conformations are selected using experimental (e.g. PRE, chemical shifts, RDC, SAXS) constraints. Preliminary experiments suggest that selleck kinase inhibitor meta-structure sequence alignments to sequences taken from the PDB structural database can indeed provide valuable information about hidden similarities and reveal structural building blocks in IDPs that can be subsequently used to improve the quality of the obtained conformational ensembles. IDPs display significant structural plasticity and undergo large structural rearrangements of the

time-averaged conformational ensemble. Therefore, they seriously challenge Cell press classical structural biology that, historically, emphasized only structural aspects of proteins, the spatial arrangements of atoms in proteins and their mutual interactions resulting from a unique conformation. Proteins are characterized by a funnel-like energy landscape and thus do not exist in single conformations

but exchange between many different conformational isomers (substates). Fundamental processes or interaction events such as crystallization, protein domain exchanges (swapping), conformational adaptations (e.g. induced-fit) and broad-range binding can be explained as conformational switches (e.g. conformational selection) resulting from the ruggedness of the energy landscape. Most importantly, this conceptual view provides a unified physico-chemical description for both globular and IDPs. While stably folded, globular proteins display a smooth bottom with only few (structurally similar) minima, IDPs have very rugged energy surfaces with low barriers and a large number of accessible minima. The problem of characterizing IDPs has a parallel in the history of polymer science where the introduction of quantitative statistical mechanics models allowed for the successful explanation of the dependence of physical properties of polymeric materials on molecular weight distributions [57].