Seasonal forcing on the dynamics ofClethrionomys rufocanus: Modeling geographic gradients in population dynamics

We interpret gradients in population dynamics of the gray-sided vole from the southwestern part of the island of Hokkaido to its northeastern part within the framework of a phenomenological model involving the relative length of summer and winter. In Hokkaido, as in other northern regions, both spring and fall is considered as short transition periods between the two main seasons — summer (the primary breeding season) and winter (the non-reproductive or secondary breeding season). We show that the geographic transition in dynamics may be understood as the combined consequence of different patterns of density-dependence during summer and winter, and geographically varying season lengths. Differences are shown to exist between summer and winter with respect to strength of density-dependence. Direct density-dependence, in particular, is stronger during winter than during summer. A model is presented to show how relative lengths of seasons can induce both stable and periodically fluctuating population dynamics. The results are compared and contrasted with what is otherwise known about the gradient in rodent dynamics in Fennoscandia.     

Measure dynamics on a one-dimensional continuous trait space: theoretical foundations for adaptive dynamics

The measure dynamics approach to modelling single-species coevolution with a one-dimensional trait space is developed and compared to more traditional methods of adaptive dynamics and the Maximum Principle. It is assumed that individual fitness results from pairwise interactions together with a background fitness that depends only on total population size. When fitness functions are quadratic in the real variables parameterizing the one-dimensional traits of interacting individuals, the following results are derived. It is shown that among monomorphisms (i.e. measures supported on a single trait value), the continuously stable strategy (CSS) characterize those that are Lyapunov stable and attract all initial measures supported in an interval containing this trait value. In the cases where adaptive dynamics predicts evolutionary branching, convergence to a dimorphism is established. Extensions of these results to general fitness functions and/or multi-dimensional trait space are discussed.     

Knottin cyclization: impact on structure and dynamics

Background  

Present in various species, the knottins (also referred to as inhibitor cystine knots) constitute a group of extremely stable miniproteins with a plethora of biological activities. Owing to their small size and their high stability, knottins are considered as excellent leads or scaffolds in drug design. Two knottin families contain macrocyclic compounds, namely the cyclotides and the squash inhibitors. The cyclotide family nearly exclusively contains head-to-tail cyclized members. On the other hand, the squash family predominantly contains linear members. Head-to-tail cyclization is intuitively expected to improve bioactivities by increasing stability and lowering flexibility as well as sensitivity to proteolytic attack.     

Host specificity dynamics: observations on gyrodactylid monogeneans

The directly transmitted viviparous gyrodactylids have high species richness but low morphological and biological diversity, and many species are recorded from only a single host. They therefore constitute a guild of species ideal for studies of the evolutionary significance of host specificity. The group has the widest host range of any monogenean family, being found on 19 orders of bony fish. However, individual species range from narrowly specific (71% of 402 described species recorded from a single host) to extremely catholic (Gyrodactylus alviga recorded from 16 hosts). Gyrodactylid-host interactions extend from 60 mya (G. lotae, G. lucii) down to 150 years (G. derjavini on Oncorhynchus mykiss). Co-evolution with the host is comparatively rare within the gyrodactylids, but host switching or ecological transfer is common, and has been facilitated by the mixing of fish strains that followed glaciation. In this review, we consider the factors responsible for gyrodactylid specificity patterns, using examples from our work on salmonid gyrodactylids including G. salaris, responsible for major epidemics on wild Atlantic salmon (Salmo salar) in Norway since 1975, and G. thymalli from grayling and G. derjavini from trout.G. salaris has a wide host range with highest population growth rates on Norwegian salmon strains. However, growth rates are variable on both host strains and species, because of the multitude of micro- and macro-environmental factors influencing parasite mortality and fecundity. A better predictor of performance is the proportion of fishes of a strain which are innately resistant to the parasite, a measure which is negatively correlated with the time to peak infection in a host strain. Population growth rate is also negatively correlated with age of infection; the initial rate, therefore, predicts best the suitability of a fish as host for G. salaris. The host response to gyrodactylids appears to be the same mechanism in all salmonids with innate resistance as one end of a spectrum, but influenced by stress and probably under polygenic control. Hybrid experiments show that performance of G. salaris on a host is heritable, and usually intermediate between that of the parents. This host response mechanism, coupled with the initial parasite population growth on a fish, determines the host specificity, i.e. whether the fish will be susceptible, a responder or innately resistant. The use of population growth rate parameters allows comparison of different hosts as a resource for a gyrodactylid. In the case of G. salaris, East Atlantic and Baltic strains of Atlantic salmon are core hosts, but other salmonids can physiologically sustain infections for considerable periods, and may be important in parasite dispersal and transmission. A further group of non-salmonid fishes are unable to sustain G. salaris reproduction, but can act as transport hosts.Population growth parameters are very labile to stressors and environmental factors, particularly temperature and salinity, and also other aspects of host ecology and water quality. These factors may also influence the spectrum of hosts that can be infected under particular conditions, and probably favoured ecological transfer of gyrodactylids between host species in periglacial conditions. G. salaris may still be undergoing post-glacial range expansion (aided by anthropogenic spread) as shown by the increase in the species range over the last 25 years. The origin of G. salaris, G. teuchis and G. thymalli is discussed in relation to glacial refugiums during the last ice age.     

OmpA: Gating and dynamics via molecular dynamics simulations

Outer membrane proteins (OMPs) of Gram-negative bacteria have a variety of functions including passive transport, active transport, catalysis, pathogenesis and signal transduction. Whilst the structures of ∼ 25 OMPs are currently known, there is relatively little known about their dynamics in different environments. The outer membrane protein, OmpA from Escherichia coli has been studied extensively in different environments both experimentally and computationally, and thus provides an ideal test case for the study of the dynamics and environmental interactions of outer membrane proteins. We review molecular dynamics simulations of OmpA and its homologues in a variety of different environments and discuss possible mechanisms of pore gating. The transmembrane domain of E. coli OmpA shows subtle differences in dynamics and interactions between a detergent micelle and a lipid bilayer environment. Simulations of the crystallographic unit cell reveal a micelle-like network of detergent molecules interacting with the protein monomers. Simulation and modelling studies emphasise the role of an electrostatic-switch mechanism in the pore-gating mechanism. Simulation studies have been extended to comparative models of OmpA homologues from Pseudomonas aeruginosa (OprF) and Pasteurella multocida (PmOmpA), the latter model including the periplasmic C-terminal domain.     

Kinetochore dynamics: how protein dynamics affect chromosome segregation

Protein dynamics generate adaptive cellular architecture. This concept is exemplified by kinetochores, organelles that orchestrate chromosome segregation during mitosis. In this review, we will focus on protein dynamics at kinetochores and discuss how these dynamics impact chromosome motility during mitosis.     

Multiply accelerated ReaxFF molecular dynamics: coupling parallel replica dynamics with collective variable hyper dynamics

ABSTRACT

To tackle the time scales required to study complex chemical reactions, methods performing accelerated molecular dynamics are necessary even with the recent advancement in high-performance computing. A number of different acceleration techniques are available. Here we explore potential synergies between two popular acceleration methods – Parallel Replica Dynamics (PRD) and Collective Variable Hyperdynamics (CVHD), by analysing the speedup obtained for the pyrolysis of n-dodecane. We observe that PRD?+?CVHD provides additional speedup to CVHD by reaching the required time scales for the reaction at an earlier wall-clock time. Although some speedup is obtained with the additional replicas, we found that the effectiveness of the inclusion of PRD is depreciated for systems where there is a dramatic increase in reaction rates induced by CVHD. Similar observations were made in the simulation of ethylene-carbonate/Li system, which is inherently more reactive than pyrolysis, indicate that the speedup obtained via the combination of the two acceleration methods can be generalised to most practical chemical systems.     

Conformational dynamics of RNA-peptide binding: a molecular dynamics simulation study

Molecular dynamics simulations of the binding of the heterochiral tripeptide KkN to the transactivation responsive (TAR) RNA of HIV-1 is presented, using an all-atom force field with explicit water. To obtain starting structures for the TAR-KkN complex, semirigid docking calculations were performed that employ an NMR structure of free TAR RNA. The molecular dynamics simulations show that the starting structures in which KkN binds to the major groove of TAR (as it is the case for the Tat-TAR complex of HIV-1) are unstable. On the other hand, the minor-groove starting structures are found to lead to several binding modes, which are stabilized by a complex interplay of stacking, hydrogen bonding, and electrostatic interactions. Although the ligand does not occupy the binding position of Tat protein, it is shown to hinder the interhelical motion of free TAR RNA. The latter is presumably necessary to achieve the conformational change of TAR RNA to bind Tat protein. Considering the time evolution of the trajectories, the binding process is found to be ligand-induced and cooperative. That is, the conformational rearrangement only occurs in the presence of the ligand and the concerted motion of the ligand and a large part of the RNA binding site is necessary to achieve the final low-energy binding state.     

The impact of rapid evolution on population dynamics in the wild: experimental test of eco-evolutionary dynamics

Rapid evolution challenges the assumption that evolution is too slow to impact short-term ecological dynamics. This insight motivates the study of 'Eco-Evolutionary Dynamics' or how evolution and ecological processes reciprocally interact on short time scales. We tested how rapid evolution impacts concurrent population dynamics using an aphid (Myzus persicae) and an undomesticated host (Hirschfeldia incana) in replicated wild populations. We manipulated evolvability by creating non-evolving (single clone) and potentially evolving (two-clone) aphid populations that contained genetic variation in intrinsic growth rate. We observed significant evolution in two-clone populations whether or not they were exposed to predators and competitors. Evolving populations grew up to 42% faster and attained up to 67% higher density, compared with non-evolving control populations but only in treatments exposed to competitors and predators. Increased density also correlates with relative fitness of competing clones suggesting a full eco-evolutionary dynamic cycle defined as reciprocal interactions between evolution and density.     

Macroevolution: dynamics of diversity

The fossil record typically exhibits very dynamic patterns of innovation, diversification and extinction. In contrast, molecular phylogenies suggest smoother patterns of evolutionary change. Several new studies reconcile this difference and reveal more about the mechanisms behind macroevolutionary change.     

Effect of molecular confinement on internal enzyme dynamics: frequency domain fluorometry and molecular dynamics simulation studies

The tryptophanyl emission decay of the mesophilic beta-galactosidase from Aspergillus oryzae free in buffer and entrapped in agarose gel is investigated as a function of temperature and compared to that of the hyperthermophilic enzyme from Sulfolobus solfataricus. Both enzymes are tetrameric proteins with a large number of tryptophanyl residues, so the fluorescence emission can provide information on the conformational dynamics of the overall protein structure rather than that of the local environment. The tryptophanyl emission decays are best fitted by bimodal Lorentzian distributions. The long-lived component is ascribed to close, deeply buried tryptophanyl residues with reduced mobility; the short-lived one arises from tryptophanyl residues located in more flexible external regions of each subunit, some of which are involved in forming the catalytic site. The center of both lifetime distribution components at each temperature increases when going from the free in solution mesophilic enzyme to the gel-entrapped and hyperthermophilic enzyme, thus indicating that confinement of the mesophilic enzyme in the agarose gel limits the freedom of the polypeptide chain. A more complex dependence is observed for the distribution widths. Computer modeling techniques are used to recognize that the catalytic sites are similar for the mesophilic and hyperthermophilic beta-galactosidases. The effect due to gel entrapment is considered in dynamic simulations by imposing harmonic restraints to solvent-exposed atoms of the protein with the exclusion of those around the active site. The temperature dependence of the tryptophanyl fluorescence emission decay and the dynamic simulation confirm that more rigid structures, as in the case of the immobilized and/or hyperthermophilic enzyme, require higher temperatures to achieve the requisite conformational dynamics for an effective catalytic action and strongly suggest a link between conformational rigidity and enhanced thermal stability.     

Effect of glycosylation on structure and dynamics of MHC class I glycoprotein: a molecular dynamics study

Complex carbohydrates linked to glycoproteins are recently being implicated to play a variety of biological roles. The lack of well-resolved crystallographic coordinates of the carbohydrates makes it difficult to assess the contributions of the glycan chain on protein structure and dynamics. We have modeled two different oligosaccharides NeuNAc2Gal3Man3GlcNAc5Fuc and Man3GlcNAc4 to generate two glycosylation variants of major histocompatibility complex (MHC) class I glycoprotein. Molecular dynamics simulations of the isolated fourteen- and seven-residue oligosaccharides have been done in vacuo and in solution. The dynamics of the two glycoforms of MHC class I protein have been simulated in solution in the free as well as in the peptide-bound form. Good agreement between the calculated solution conformations of the oligosaccharides in isolated and conjugated forms and the average conformations obtained from x-ray or NMR data was observed for most of the glycosidic linkages. These molecular dynamics simulations of the isolated glycan chains and the glycoconjugates reveal the details of the conformational flexibility of the glycan chains; they also provide atomic level details of protein-carbohydrate interactions and the effect of the ligand binding on the carbohydrate structure and dynamics. It was found that though there is some flexibility in some of the glycosidic linkages in the isolated oligosaccharides, in the protein-conjugated form the linkages adopt more restricted conformations. The glycan chains protrude out into the solvent and might hinder the lateral association of the proteins. The presence of the bulky glycan chains does not affect the average backbone fold of the protein but induces local changes in protein structure and dynamics. It has been noted that the extent of the changes depends upon the nature of the attached glycan chain. The glycan chains do not appear to influence the peptide binding property of the protein directly, but may stabilize the protein residues that are involved in ligand binding.     

Studying reactive processes with classical dynamics: rebinding dynamics in MbNO

A new surface-crossing algorithm suitable for describing bond-breaking and bond-forming processes in molecular dynamics simulations is presented. The method is formulated for two intersecting potential energy manifolds which dissociate to different adiabatic states. During simulations, crossings are detected by monitoring an energy criterion. If fulfilled, the two manifolds are mixed over a finite number of time steps, after which the system is propagated on the second adiabat and the crossing is carried out with probability one. The algorithm is extensively tested (almost 0.5 mus of total simulation time) for the rebinding of NO to myoglobin. The unbound surface (Fe...NO) is represented using a standard force field, whereas the bound surface (Fe-NO) is described by an ab initio potential energy surface. The rebinding is found to be nonexponential in time, in agreement with experimental studies, and can be described using two time constants. Depending on the asymptotic energy separation between the manifolds, the short rebinding timescale is between 1 and 9 ps, whereas the longer timescale is about an order of magnitude larger. NO molecules which do not rebind within 1 ns are typically found in the Xenon-4 pocket, indicating the high affinity of NO to this region in the protein.