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

Induced fit, conformational selection and independent dynamic segments: an extended view of binding events

Single molecule and NMR measurements of protein dynamics increasingly uncover the complexity of binding scenarios. Here we describe an extended conformational selection model which embraces a repertoire of selection and adjustment processes. Induced fit can be viewed as a subset of this repertoire, whose contribution is affected by the bond-types stabilizing the interaction and the differences between the interacting partners. We argue that protein segments whose dynamics are distinct from the rest of the protein ('discrete breathers') can govern conformational transitions and allosteric propagation that accompany binding processes, and as such may be more sensitive to mutational events. Additionally, we highlight the dynamic complexity of binding scenarios as they relate to events such as aggregation and signalling, and the crowded cellular environment.Comment: 9 pages, 2 Figures, 1 Table, 2 boxes, Trends in Biochemical Sciences 2010 October issue cover stor

Coevolutionary games - a mini review

Prevalence of cooperation within groups of selfish individuals is puzzling in that it contradicts with the basic premise of natural selection. Favoring players with higher fitness, the latter is key for understanding the challenges faced by cooperators when competing with defectors. Evolutionary game theory provides a competent theoretical framework for addressing the subtleties of cooperation in such situations, which are known as social dilemmas. Recent advances point towards the fact that the evolution of strategies alone may be insufficient to fully exploit the benefits offered by cooperative behavior. Indeed, while spatial structure and heterogeneity, for example, have been recognized as potent promoters of cooperation, coevolutionary rules can extend the potentials of such entities further, and even more importantly, lead to the understanding of their emergence. The introduction of coevolutionary rules to evolutionary games implies, that besides the evolution of strategies, another property may simultaneously be subject to evolution as well. Coevolutionary rules may affect the interaction network, the reproduction capability of players, their reputation, mobility or age. Here we review recent works on evolutionary games incorporating coevolutionary rules, as well as give a didactic description of potential pitfalls and misconceptions associated with the subject. In addition, we briefly outline directions for future research that we feel are promising, thereby particularly focusing on dynamical effects of coevolutionary rules on the evolution of cooperation, which are still widely open to research and thus hold promise of exciting new discoveries.Comment: 24 two-column pages, 10 figures; accepted for publication in BioSystem

Potential application of network descriptions for understanding conformational changes and protonation states of ABC transporters.

The ABC (ATP Binding Cassette) transporter protein superfamily comprises a large number of ubiquitous and functionally versatile proteins conserved from archaea to humans. ABC transporters have a key role in many human diseases and also in the development of multidrug resistance in cancer and in parasites. Although a dramatic progress has been achieved in ABC protein studies in the last decades, we are still far from a detailed understanding of their molecular functions. Several aspects of pharmacological ABC transporter targeting also remain unclear. Here we summarize the conformational and protonation changes of ABC transporters and the potential use of this information in pharmacological design. Network related methods, which recently became useful tools to describe protein structure and dynamics, have not been applied to study allosteric coupling in ABC proteins as yet. A detailed description of the strengths and limitations of these methods is given, and their potential use in describing ABC transporter dynamics is outlined. Finally, we highlight possible future aspects of pharmacological utilization of network methods and outline the future trends of this exciting field

Effects of adaptive degrees of trust on coevolution of quantum strategies on scale-free networks

We study the impact of adaptive degrees of trust on the evolution of cooperation in the quantum prisoner's dilemma game. In addition to the strategies, links between players are also subject to evolution. Starting with a scale-free interaction network, players adjust trust towards their neighbors based on received payoffs. The latter governs the strategy adoption process, while trust governs the rewiring of links. As soon as the degree of trust towards a neighbor drops to zero, the link is rewired to another randomly chosen player within the network. We find that for small temptations to defect cooperators always dominate, while for intermediate and strong temptations a single quantum strategy is able to outperform all other strategies. In general, reciprocal trust remains within close relationships and favors the dominance of a single strategy. Due to coevolution, the power-law degree distributions transform to Poisson distributions.Qiang Li, Minyou Chen, Matjaz Perc, Azhar Iqbal, & Derek Abbot

Games network and application to PAs system.

International audienceIn this article, we present a game theory based framework, named games network, for modeling biological interactions. After introducing the theory, we more precisely describe the methodology to model biological interactions. Then we apply it to the plasminogen activator system (PAs) which is a signal transduction pathway involved in cancer cell migration. The games network theory extends game theory by including the locality of interactions. Each game in a games network represents local interactions between biological agents. The PAs system is implicated in cytoskeleton modifications via regulation of actin and microtubules, which in turn favors cell migration. The games network model has enabled us a better understanding of the regulation involved in the PAs system