Identifying mechanistically distinct pathways in kinetic transition networks.

We present an implementation of a scalable path deviation algorithm to find the k most kinetically relevant paths in a transition network, where each path is distinguished on the basis of having a distinct rate-limiting edge. The potential of the algorithm to identify distinct pathways that exist in separate regions of the configuration space is demonstrated for two benchmark systems with double-funnel energy landscapes, namely a model "three-hole" network embedded on a 2D potential energy surface and the cluster of 38 Lennard-Jones atoms (LJ38). The path cost profiles for the interbasin transitions of the two systems reflect the contrasting nature of the landscapes. There are multiple well-defined pathway ensembles for the three-hole system, whereas the transition in LJ38 effectively involves a single ensemble of pathways via disordered structures. A by-product of the algorithm is a set of edges that constitute a cut of the network, which is related to the discrete analog of a transition dividing surface. The algorithm ought to be useful for determining the existence, or otherwise, of competing mechanisms in large stochastic network models of dynamical processes and for assessing the kinetic relevance of distinguishable ensembles of pathways. This capability will provide insight into conformational transitions in biomolecules and other complex slow processes.DJS gratefully acknowledges the Cambridge Commonwealth, European and International Trust for a PhD scholarship. DJW gratefully acknowledges support from the EPSRC

Graph transformation and shortest paths algorithms for finite Markov chains.

The graph transformation (GT) algorithm robustly computes the mean first-passage time to an absorbing state in a finite Markov chain. Here we present a concise overview of the iterative and block formulations of the GT procedure and generalize the GT formalism to the case of any path property that is a sum of contributions from individual transitions. In particular, we examine the path action, which directly relates to the path probability, and analyze the first-passage path ensemble for a model Markov chain that is metastable and therefore numerically challenging. We compare the mean first-passage path action, obtained using GT, with the full path action probability distribution simulated efficiently using kinetic path sampling, and with values for the highest-probability paths determined by the recursive enumeration algorithm (REA). In Markov chains representing realistic dynamical processes, the probability distributions of first-passage path properties are typically fat-tailed and therefore difficult to converge by sampling, which motivates the use of exact and numerically stable approaches to compute the expectation. We find that the kinetic relevance of the set of highest-probability paths depends strongly on the metastability of the Markov chain, and so the properties of the dominant first-passage paths may be unrepresentative of the global dynamics. Use of a global measure for edge costs in the REA, based on net productive fluxes, allows the total reactive flux to be decomposed into a finite set of contributions from simple flux paths. By considering transition flux paths, a detailed quantitative analysis of the relative importance of competing dynamical processes is possible even in the metastable regime.EPSR

Energy Landscapes of Deoxyxylo- and Xylo-Nucleic Acid Octamers.

Artificial analogues of the natural nucleic acids have attracted interest as a diverse class of information storage molecules capable of self-replication. In this study, we use the computational potential energy landscape framework to investigate the structural and dynamical properties of xylo- and deoxyxylo-nucleic acids (XyNA and dXyNA), which are derived from their respective RNA and DNA analogues by inversion of a single chiral center in the sugar moiety of the nucleotides. For an octameric XyNA sequence and the analogue dXyNA, we observe facile conformational transitions between a left-handed helix, which is the free energy global minimum, and a ladder-type structure with approximately zero helicity. The competing ensembles are better separated in the dXyNA, making it a more suitable candidate for a molecular switch, whereas the XyNA exhibits additional flexibility. Both energy landscapes exhibit greater frustration than we observe in RNA or DNA, in agreement with the higher degree of optimization expected from the principle of minimal frustration in evolved biomolecules

Energy Landscapes and Hybridization Pathways for DNA Hexamer Duplexes.

Strand hybridization is not only a fundamental molecular mechanism underlying the biological functions of nucleic acids but is also a key step in the design of efficient nanodevices. Despite recent efforts, the microscopic rules governing the hybridization mechanisms remain largely unknown. In this study, we exploit the energy landscape framework to assess how sequence-specificity modulates the hybridization mechanisms in DNA. We find that GG-tracts hybridize much more rapidly compared to GC-tracts, via either zippering or slithering pathways. For the hybridization of GG-tracts, both zippering and slithering mechanisms appear to be kinetically relevant. In contrast, for the GC-tracts, the zippering mechanism is dominant. Our work reveals that even for the relatively small systems considered, the energy landscapes feature multiple metastable states and kinetic traps, which is at odds with the conventional "all-or-nothing" model of DNA hybridization formulated on the basis of thermodynamic arguments alone. Interestingly, entropic effects are found to play an important role in determining the thermal stability of competing conformational ensembles and in determining the preferred hybridization pathways.epsr

Partial Flavor Symmetry Restoration for Chiral Staggered Fermions

We study the leading discretization errors for staggered fermions by first constructing the continuum effective Lagrangian including terms of O(a^2), and then constructing the corresponding effective chiral Lagrangian. The terms of O(a^2) in the continuum effective Lagrangian completely break the SU(4) flavor symmetry down to the discrete subgroup respected by the lattice theory. We find, however, that the O(a^2) terms in the potential of the chiral Lagrangian maintain an SO(4) subgroup of SU(4). It follows that the leading discretization errors in the pion masses are SO(4) symmetric, implying three degeneracies within the seven lattice irreducible representations. These predictions hold also for perturbatively improved versions of the action. These degeneracies are observed, to a surprising degree of accuracy, in existing data. We argue that the SO(4) symmetry does not extend to the masses and interactions of other hadrons (vector mesons, baryons, etc), nor to higher order in a^2. We show how it is possible that, for physical quark masses of O(a^2), the new SO(4) symmetry can be spontaneously broken, leading to a staggered analogue of the Aoki-phase of Wilson fermions. This does not, however, appear to happen for presently studied versions of the staggered action.Comment: 26 pages, 2 figures (using psfig). Version to appear in PRD (clarifications added to introduction and section 6; typos corrected; references updated

Hadronic Electromagnetic Properties at Finite Lattice Spacing

Electromagnetic properties of the octet mesons as well as the octet and decuplet baryons are augmented in quenched and partially quenched chiral perturbation theory to include O(a) corrections due to lattice discretization. We present the results for the SU(3) flavor group in the isospin limit as well as the results for SU(2) flavor with non-degenerate quarks. These corrections will be useful for extrapolation of lattice calculations using Wilson valence and sea quarks, as well as calculations using Wilson sea quarks and Ginsparg-Wilson valence quarks.Comment: 19 pages, 0 figures, RevTeX

Hadron Spectrum with Wilson fermions

We present results of a high statistics study of the quenched spectrum using Wilson fermions at $\beta=6.0$ on $32^3 \times 64$ lattices. We calculate the masses of mesons and baryons composed of both degenerate and non-degenerate quarks. Using non-degenerate quark combinations allows us to study baryon mass splittings in detail. We find significant deviations from the lowest order chiral expansion, deviations that are consistent with the expectations of quenched chiral perturbation theory. We find that there is a $\sim 20$ systematic error in the extracted value of $m_s$, depending on the meson mass ratio used to set its value. Using the largest estimate of $m_s$ we find that the extrapolated octet mass-splittings are in agreement with the experimental values, as is $M_\Delta - M_N$, while the decuplet splittings are 30% smaller than experiment. Combining our results with data from the GF11 collaboration we find considerable ambiguity in the extrapolation to the continuum limit. Our preferred values are $M_N / M_\rho = 1.38(7)$ and $M_\Delta / M_\rho = 1.73(10)$, suggesting that the quenched approximation is good to only $\sim 10-15$. We also analyze the $O(ma)$ discretization errors in heavy quark masses.Comment: 52 pages. Tex. Modified "axis" source for figures also included. Needs macro packages lanlmac and epsf. Uses hyperbasics if available. Significant number of typographical errors correcte

One Spin Trace Formalism for BK B_K

It has been known for some time that there are two methods to calculate $B_K$ with staggered fermions: one is the two spin trace formalism and the other is the one spin trace formalism. Until now, the two spin trace formalism has been exclusively used for weak matrix element calculations with staggered fermions. Here, the one spin trace formalism to calculate $B_K$ with staggered fermions is explained. It is shown that the one spin trace operators require additional chiral partner operators in order to keep the continuum chiral behavior. The renormalization of the one spin trace operators is described and compared with the two spin trace formalism.Comment: 47 pages, latex, 4 figures are available on reques

Baryon Decuplet to Octet Electromagnetic Transitions in Quenched and Partially Quenched Chiral Perturbation Theory

We calculate baryon decuplet to octet electromagnetic transition form factors in quenched and partially quenched chiral perturbation theory. We work in the isospin limit of SU(3) flavor, up to next-to-leading order in the chiral expansion, and to leading order in the heavy baryon expansion. Our results are necessary for proper extrapolation of lattice calculations of these transitions. We also derive expressions for the case of SU(2) flavor away from the isospin limit.Comment: 16 pages, 3 figures, revtex