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Transition Pathways (transition + pathway)
Selected AbstractsOn searching in, sampling of, and dynamically moving through conformational space of biomolecular systems: A reviewJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 2 2008Markus Christen Abstract Methods to search for low-energy conformations, to generate a Boltzmann-weighted ensemble of configurations, or to generate classical-dynamical trajectories for molecular systems in the condensed liquid phase are briefly reviewed with an eye to application to biomolecular systems. After having chosen the degrees of freedom and method to generate molecular configurations, the efficiency of the search or sampling can be enhanced in various ways: (i) efficient calculation of the energy function and forces, (ii) application of a plethora of search enhancement techniques, (iii) use of a biasing potential energy term, and (iv) guiding the sampling using a reaction or transition pathway. The overview of the available methods should help the reader to choose the combination that is most suitable for the biomolecular system, degrees of freedom, interaction function, and molecular or thermodynamic properties of interest. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008 [source] Src kinase activation: A switched electrostatic networkPROTEIN SCIENCE, Issue 5 2006Elif Ozkirimli Abstract Src tyrosine kinases are essential in numerous cell signaling pathways, and improper functioning of these enzymes has been implicated in many diseases. The activity of Src kinases is regulated by conformational activation, which involves several structural changes within the catalytic domain (CD): the orientation of two lobes of CD; rearrangement of the activation loop (A-loop); and movement of an ,-helix (,C), which is located at the interface between the two lobes, into or away from the catalytic cleft. Conformational activation was investigated using biased molecular dynamics to explore the transition pathway between the active and the down-regulated conformation of CD for the Src-kinase family member Lyn kinase, and to gain insight into the interdependence of these changes. Lobe opening is observed to be a facile motion, whereas movement of the A-loop motion is more complex requiring secondary structure changes as well as communication with ,C. A key result is that the conformational transition involves a switch in an electrostatic network of six polar residues between the active and the down-regulated conformations. The exchange between interactions links the three main motions of the CD. Kinetic experiments that would demonstrate the contribution of the switched electrostatic network to the enzyme mechanism are proposed. Possible implications for regulation conferred by interdomain interactions are also discussed. [source] Guest-dependent conformation of 18-crown-6 tetracarboxylic acid: Relation to chiral separation of racemic amino acidsCHIRALITY, Issue 7 2008Hiroomi Nagata Abstract (+)-18-Crown-6 tetracarboxylic acid (18C6H4) has been used as a chiral selector for various amines and amino acids. To further clarify the structural scaffold of 18C6H4 for chiral separation, single crystal X-ray analysis of its glycine+ (1), H3O+ (2), H5O (3), NH (4), and 2CH3NH (5) complexes was performed and the guest-dependent conformation of 18C6H4 was investigated. The crown ether ring of 18C6H4 in 3, 4, and 5 took a symmetrical C2 or C2 -like conformation, whereas that in 1 and 2 took an asymmetric C1 conformation, which is commonly observed in complexes with various optically active amino acids. The overall survey of the present and related complexes suggests that the molecular conformation of 18C6H4 is freely changeable within an allowable range, depending on the molecular shape and interaction mode with the cationic guest. On the basis of the present results, we propose the allowable conformational variation of 18C6H4 and a possible transition pathway from its primary conformation to the conformation suitable for chiral separation of racemic amines and amino acids. Chirality, 2008. © 2008 Wiley-Liss, Inc. [source] Youth Transitions and Employment in GermanyINTERNATIONAL SOCIAL SCIENCE JOURNAL, Issue 164 2000Walter R. Heinz In the 1990s, the timing and duration of youth transitions has become variable because of cultural modernisation and the declining stability of careers. In particular, the German ,dual system' of Vocational Education and Training (VET) has come under pressure of globalisation and labour market deregulation. Despite economic turbulence, the main features of the VET have been maintained. The apprenticeship route is still highly accepted-two-thirds of the cohort of school-leavers are passing through it. It continues to provide standardised occupational qualifications and a context for socialisation. It supplies a skilled labour force and keeps youth unemployment low-despite shortcomings in standards of social equality and a slow pace in adapting to changes in technology and work. For the future, the ,left modernisers' strategy of upgrading skills remains possible, by reforming the apprenticeship system and main-taining the 'high-skills, route for transition from education to work. In transition studies structural analysis should be combined with research on institutional regulations, transition pathways, and individual agency. [source] Adolescents with Type 1 Diabetes: transition between diabetes servicesJOURNAL OF CLINICAL NURSING, Issue 6 2006Kate Visentin MN Aim., The research aimed to develop a sustainable and coordinated approach to facilitating the transition between diabetes services for adolescents. The objectives were to: (1) involve key diabetes health delivery stakeholders in expressing their concerns and issues about current service delivery and ways to improve same, and (2) reveal from the perspective of the adolescents living with Type 1 Diabetes their experiences surrounding the process of transition. Background., This paper presents research that sought to identify the major concerns and issues that stakeholders had about transition and to reveal the experience of transition for the adolescent with Type 1 Diabetes. Key representatives from seven public diabetes services in Adelaide, South Australia worked collaboratively to answer the objectives of this inquiry. Approach., Interview data were generated and analysed using a response focus framework provided by fourth generation evaluation research. In this study, the focus was on common concerns, claims and issues raised by health care professionals (n = 21) and adolescents (n = 10) aged between 15 and 18 years about transferring from children's to adult diabetes services. Findings., Data revealed education and dietetic advice was reactive rather than proactive and that the paediatric model of care is philosophically and practically different to the adult model of diabetes care. Three phases of transition were identified: preparation, formal transition and evaluation. Our findings indicated that these stages of transition were not being fully implemented in health units. Conclusion., The project findings have set the scene to establish a multidisciplinary working party to work collaboratively across agencies to develop effective transition pathways. Relevance to clinical practice., The role of diabetes nurse educators and dietitians in South Australia is under-used throughout the transition process. Diabetes nurse educators are in an ideal position to prepare, coordinate and evaluate transitional processes. [source] Allosteric transition pathways in the lactose repressor protein core domains: Asymmetric motions in a homodimerPROTEIN SCIENCE, Issue 11 2003Terence C. Flynn Abstract The crystal structures of lactose repressor protein (LacI) provide static endpoint views of the allosteric transition between DNA- and IPTG-bound states. To obtain an atom-by-atom description of the pathway between these two conformations, motions were simulated with targeted molecular dynamics (TMD). Strikingly, this homodimer exhibited asymmetric dynamics. All asymmetries observed in this simulation are reproducible and can begin on either of the two monomers. Asymmetry in the simulation originates around D149 and was traced back to the pre-TMD equilibrations of both conformations. In particular, hydrogen bonds between D149 and S193 adopt a variety of configurations during repetitions of this process. Changes in this region propagate through the structure via noncovalent interactions of three interconnected pathways. The changes of pathway 1 occur first on one monomer. Alterations move from the inducer-binding pocket, through the N-subdomain ,-sheet, to a hydrophobic cluster at the top of this region and then to the same cluster on the second monomer. These motions result in changes at (1) side chains that form an interface with the DNA-binding domains and (2) K84 and K84', which participate in the monomer,monomer interface. Pathway 2 reflects consequent reorganization across this subunit interface, most notably formation of a H74-H74rsquo; ,-stacking intermediate. Pathway 3 extends from the rear of the inducer-binding pocket, across a hydrogen-bond network at the bottom of the pocket, and transverses the monomer,monomer interface via changes in H74 and H74rsquo;. In general, intermediates detected in this study are not apparent in the crystal structures. Observations from the simulations are in good agreement with biochemical data and provide a spatial and sequential framework for interpreting existing genetic data. [source] A conceptual model of plant community changes following cessation of cultivation in semi-arid grasslandAPPLIED VEGETATION SCIENCE, Issue 4 2010Nathan K. Wong Abstract Question: Can vegetation changes that occur following cessation of cultivation for cereal crop production in semi-arid native grasslands be described using a conceptual model that explains plant community dynamics following disturbance? Location: Eighteen native grasslands with varying time-since-last cultivation across northern Victoria, Australia. Methods: We examined recovery of native grasslands after cessation of cultivation along a space for- time chronosequence. By documenting floristic composition and soil properties of grasslands with known cultivation histories, we established a conceptual model of the vegetation states that occur following cessation of cultivation and inferred transition pathways for community recovery. Results: Succession from an exotic-dominated grassland to native grassland followed a linear trajectory. These changes represent an increase in richness and cover of native forbs, a decrease in cover of exotic annual species and little change in native perennial graminoids and exotic perennial forbs. Using a state-and-transition model, two distinct vegetation states were evident: (1) an unstable, recently cultivated state, dominated by exotic annuals, and (2) a more diverse, stable state. The last-mentioned state can be divided into two further states based on species composition: (1) a never-cultivated state dominated by native perennial shrubs and grasses, and (2) a long-uncultivated state dominated by a small number of native perennial and native and exotic annual species that is best described as a subset of the never-cultivated state. Transitions between these states are hypothesized to be dependent upon landscape context, seed availability and soil recovery. Conclusions: Legacies of past land use on soils and vegetation of semi-arid grasslands are not as persistent as in other Australian communities. Recovery appears to follow a linear, directional model of post-disturbance regeneration which may be advanced by overcoming dispersal barriers hypothesised to restrict recovery. [source] Land-cover/use transitions in the binational Tijuana River watershed during a period of rapid industrializationAPPLIED VEGETATION SCIENCE, Issue 1 2008L. Ojeda-Revah Abstract Question: How do differing social and economic systems affect the dynamics and trajectory of land cover / land use change on similar, neighbouring ecosystems in a time span when an economic industrialization program was enforced? Location: Tijuana River watershed, located on the border between Baja California, Mexico and California, United States. Methods: We quantified land use changes between 1970 and 1994 in the Tijuana River watershed. Using aerial photographs and geographic information systems, we elaborated land-cover/use maps and calculated transition probability matrices to describe natural land-cover changes at the landscape level on both sides of the border. Results: Land cover / land use transitions are mainly driven by urban development on both sides of the border, but exhibit different patterns in each country. The processes seem to be more complex in the Mexican part of the basin, where itinerant land use may revert induced grasslands and rain-fed agriculture into natural communities, than on the US side, where the transition pathways are few and unidirectional. Conclusions: Despite the need for an integrated planning and management of binational basins and shared water resources, in practice, these goals may be hampered by different economic and social factors triggering land use change within each country. [source] | ||||||||||