Disordered Proteins and Network Disorder in Network Descriptions of Protein Structure, Dynamics and Function: Hypotheses and a Comprehensive Review

Abstract

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.

System Level Mechanisms of Adaptation, Learning, Memory Formation and Evolvability: The Role of Chaperone and Other Networks

“…Protein structure networks often have weighted links instead of distance cut-offs, where the edge-weight is inversely proportional with the distance between the two amino acid side chains. Covalent bonds may be included or excluded in protein structure networks [11,[29][30][31][32][33][34][35][36][37][38].…”

“…However, the cumulus state has a rather flexible inter-modular structure due to the partial dissociation of modules. From this point of view the cumulus state has a higher complexity than the stratus state [11,13,54].…”

“…Such a system has a high stress resistance. The balance between the two types of networks encoding these two segregated phenotypic behavior might be influenced (among others) by the amount of available molecular chaperones [3,11,125,126]. Importantly, neither an extreme form of the flexible stratus state, nor the extreme form of the rigid cumulus state are optimal -as it was shown by Draghi et al [121], who demonstrated that neither absolutely robust (flexible, extremely stratustype), nor absolutely non-robust (rigid, extremely cumulustype) systems are successful in attaining a fast adaptation rate.…”

“…Importantly, neither an extreme form of the flexible stratus state, nor the extreme form of the rigid cumulus state are optimal -as it was shown by Draghi et al [121], who demonstrated that neither absolutely robust (flexible, extremely stratustype), nor absolutely non-robust (rigid, extremely cumulustype) systems are successful in attaining a fast adaptation rate. Only balanced systems having both flexibility and rigidity may be successful in long-term adaptation involving both learning and memory formation processes [3,11,125,126] as we will describe in Section 4.B. in more details.…”

“…Networks often have a modular structure, i.e., groups of network nodes (also called as network communities) have denser intra-group connections than the density of the connections of the group with neighboring groups. Biological networks are often hierarchical meaning that nodes and groups have an uneven position in the hierarchical network, which divides them to a 'central core' and a 'periphery' [11,12].…”