Disordered proteins and network disorder in network descriptions of protein structure, dynamics and function. Hypotheses and a comprehensive review

During the last decade, network approaches became a powerful tool to describe protein structure and dynamics. Here we review the links between disordered proteins and the associated networks, and describe the consequences of local, mesoscopic and global network disorder on changes in protein structure and dynamics. We introduce a new classification of protein networks into ‘cumulus-type’, i.e., those similar to puffy (white) clouds, and ‘stratus-type’, i.e., those similar to flat, dense (dark) low-lying clouds, and relate these network types to protein disorder dynamics and to differences in energy transmission processes. In the first class, there is limited overlap between the modules, which implies higher rigidity of the individual units; there the conformational changes can be described by an ‘energy transfer’ mechanism. In the second class, the topology presents a compact structure with significant overlap between the modules; there the conformational changes can be described by ‘multi-trajectories’; that is, multiple highly populated pathways. We further propose that disordered protein regions evolved to help other protein segments reach ‘rarely visited’ but functionally-related states. We also show the role of disorder in ‘spatial games’ of amino acids; highlight the effects of intrinsically disordered proteins (IDPs) on cellular networks and list some possible studies linking protein disorder and protein structure networks

The Last Scientific Revolution

Critically growing problems of fundamental science organisation and content are analysed with examples from physics and emerging interdisciplinary fields. Their origin is specified and new science structure (organisation and content) is proposed as a unified solution

Exon-phase symmetry and intrinsic structural disorder promote modular evolution in the human genome

A key signature of module exchange in the genome is phase symmetry of exons, suggestive of exon shuffling events that occurred without disrupting translation reading frame. At the protein level, intrinsic structural disorder may be another key element because disordered regions often serve as functional elements that can be effectively integrated into a protein structure. Therefore, we asked whether exon-phase symmetry in the human genome and structural disorder in the human proteome are connected, signalling such evolutionary mechanisms in the assembly of multi-exon genes. We found an elevated level of structural disorder of regions encoded by symmetric exons and a preferred symmetry of exons encoding for mostly disordered regions (>70% predicted disorder). Alternatively spliced symmetric exons tend to correspond to the most disordered regions. The genes of mostly disordered proteins (>70% predicted disorder) tend to be assembled from symmetric exons, which often arise by internal tandem duplications. Preponderance of certain types of short motifs (e.g. SH3-binding motif) and domains (e.g. high-mobility group domains) suggests that certain disordered modules have been particularly effective in exon-shuffling events. Our observations suggest that structural disorder has facilitated modular assembly of complex genes in evolution of the human genome. © 2013 The Author(s)

From the end of Unitary Science Projection to the Causally Complete Complexity Science: Extended Mathematics, Solved Problems, New Organisation and Superior Purposes

The deep crisis in modern fundamental science development is ever more evident and openly recognised now even by mainstream, official science professionals and leaders. By no coincidence, it occurs in parallel to the world civilisation crisis and related global change processes, where the true power of unreduced scientific knowledge is just badly missing as the indispensable and unique tool for the emerging greater problem solution and further progress at a superior level of complex world dynamics. Here we reveal the mathematically exact reason for the crisis in conventional science, containing also the natural and unified problem solution in the form of well-specified extension of usual, artificially restricted paradigm. We show how that extended, now causally complete science content provides various "unsolvable" problem solutions and opens new development possibilities for both science and society, where the former plays the role of the main, direct driver for the latter. We outline the related qualitative changes in science organisation, practice and purposes, giving rise to the sustainability transition in the entire civilisation dynamics towards the well-specified superior level of its unreduced, now well understood and universally defined complexity

Finite-Size Studies on the SO(5) Symmetry of the Hubbard Model

We present numerical evidence for the approximate SO(5) symmetry of the Hubbard model on a 10 site cluster. Various dynamic correlation functions involving the $\pi$ operators, the generators of the SO(5) algebra, are studied using exact diagonalisation, and are found to possess sharp collective peaks. Our numerical results also lend support on the interpretation of the recent resonant neutron scattering peaks in the YBCO superconductors in terms of the Goldstone modes of the spontaneously broken SO(5) symmetry.Comment: 4 pages, Rev-Tex, includes 2 eps figure