Multiple Transition Pathways Research Articles

The roles and dynamics of transition intermediaries in enabling sustainable public food procurement: insights from Spain

Abstract Sustainable Public Food Procurement (SPFP) is gaining recognition for its potential to improve the sustainability of food systems and promote healthier diets. However, SPFP faces various challenges, including coordination issues, actor dynamics, infrastructure limitations, unsustainable habits, and institutional resistance, among others. Drawing upon insights from the Multi-Level Perspective (MLP) on socio-technical transitions and the X-curve model on transition dynamics, this study investigates the role of transition intermediaries in facilitating SPFP-induced transformations in food systems. Focusing on four case studies in Spain, we identify common barriers encountered in SPFP and analyse how distinct types of transition intermediaries contribute individually and collectively to address these challenges. Additionally, we explore how intermediary networks evolve throughout different phases of the transition process. Our findings reveal that SPFP barriers are systemic and interconnected, emphasizing the necessity of collective intermediation to overcome these obstacles. Furthermore, our results reveal how collective intermediation is orchestrated by pivotal intermediaries who mobilize diverse transition intermediaries, shaping multiple transition pathways. These intermediaries operate at both food system regimes and niches, challenging the conventional notion that transformative change can only originate from niche efforts. Lastly, we highlight the dynamic and flexible nature of intermediation in SPFP transitions, underscoring the importance of adaptability in strategies as these transitions evolve over time. Practical implications include the need for context-specific, adaptive approaches and strategies that leverage intermediary diversity. This research offers insights for policymakers, practitioners, and scholars into SPFP and broader transitions towards food systems transformation, fostering a more comprehensive understanding of these transition processes.

Bifurcation instructed design of multistate machines

We propose a design paradigm for multistate machines where transitions from one state to another are organized by bifurcations of multiple equilibria of the energy landscape describing the collective interactions of the machine components. This design paradigm is attractive since, near bifurcations, small variations in a few control parameters can result in large changes to the system's state providing an emergent lever mechanism. Further, the topological configuration of transitions between states near such bifurcations ensures robust operation, making the machine less sensitive to fabrication errors and noise. To design such machines, we develop and implement a new efficient algorithm that searches for interactions between the machine components that give rise to energy landscapes with these bifurcation structures. We demonstrate a proof of concept for this approach by designing magnetoelastic machines whose motions are primarily guided by their magnetic energy landscapes and show that by operating near bifurcations we can achieve multiple transition pathways between states. This proof of concept demonstration illustrates the power of this approach, which could be especially useful for soft robotics and at the microscale where typical macroscale designs are difficult to implement.

Efficient discovery of multiple minimum action pathways using Gaussian process

We present a new efficient transition pathway search method based on the least action principle and the Gaussian process regression method. Most pathway search methods developed so far rely on string representations, which approximate a transition pathway by a series of slowly varying system replicas. Such string methods are computationally expensive in general because they require many replicas to obtain smooth pathways. Here, we present an approach employing the Gaussian process regression method, which infers the shape of a potential energy surface with a few observed data and Gaussian-shaped kernel functions. We demonstrate a drastic elevation of computing efficiency of the method about five orders of magnitude than existing methods. Further, to demonstrate its real-world capabilities, we apply our method to find multiple conformational transition pathways of alanine dipeptide using a quantum mechanical potential. Owing to the improved efficiency of our method, Gaussian process action optimization (GPAO), we obtain the multiple transition pathways of alanine dipeptide and calculate their transition probabilities successfully with density-functional theory (DFT) accuracy. In addition, GPAO successfully finds the isomerization pathways of small molecules and the rearrangement of atoms on a metallic surface.

Coarse-Grained Modeling of Multiple Pathways in Conformational Transitions of Multi-Domain Proteins.

Large-scale conformational transitions in multi-domain proteins are often essential for their functions. To investigate the transitions, it is necessary to explore multiple potential pathways, which involve different intermediate structures. Here, we present a multi-basin (MB) coarse-grained (CG) structure-based Go̅ model for describing transitions in proteins with more than two moving domains. This model is an extension of our dual-basin Go̅ model in which system-dependent parameters are determined systematically using the multistate Bennett acceptance ratio method. In the MB Go̅ model for multi-domain proteins, we assume that intermediate structures may have partial inter-domain native contacts. This approach allows us to search multiple transition pathways that involve distinct intermediate structures using the CG molecular dynamics (MD) simulations. We apply this scheme to an enzyme, adenylate kinase (AdK), which has three major domains and can move along two different pathways. Using the optimized mixing parameters for each pathway, AdK shows frequent transitions between the Open, Closed, and the intermediate basins and samples a wide variety of conformations within each basin. The explored multiple transition pathways could be compared with experimental data and examined in more detail by atomistic MD simulations.

Quantitative relationship between low-carbon pathways and system transition costs based on a multi-period and multi-regional energy infrastructure planning approach: A case study of China

Low-carbon transition would trigger huge costs from reshaping complex energy systems due to large-scale renewable energy investment and early retirement of fossil-energy infrastructure. Reducing costs is challenging, because multiple transition pathways, comprised of massive transition policies and their schedule and pace, would lead to variation on system transition costs, despite achieving the same transition degree. In this paper, we aim to explore a proper pathway with lower costs towards the same transition degree, whilst previous studies focus on impacts of achieving different transition targets. A multi-regional, multi-period, infrastructure-based model is applied to quantify system transition costs, and China is taken as a case study. Scenarios, describing representative pathways to the same transition degree, are designed to establish quantitative relationship between pathways and costs. Results show that, for coal-dominated countries, approaching marginal cost balance of deep electrification and intensive non-fossil power penetration would lead to lower costs. An improper pathway would raise system transition costs up by 17% than a proper pathway we present, whilst this proper pathway would still lead to 35% more costs than the reference scenario. Furthermore, specific infrastructure deployment recommendations are discussed to make the pathway feasible and executive.

Fano effect in an ultracold atom-molecule coupled system

The Fano effect or Fano resonance with a characteristically asymmetric line shape originates from quantum interference between direct and indirect transition pathways in continuum-bound coupled systems, and is a ubiquitous phenomenon in atomic, molecular, nuclear and solid-state physics. In optical nanoscale structures, the Fano effect has wide-ranging applications that include optical filtering, sensing, all-optical switching, quantum interferometry and nonlinear optics, and this opens new avenues for photonic devices. The emergent area of ultracold atomic and molecular gases presents an ideal platform for studying Fano resonances, since the physical parameters of these gases can be extensively tuned with high precision using external fields. However, an experimental demonstration of the Fano effect in hybridized atom-molecular coupled systems has remained elusive. Here, we report on observations of the Fano effect in molecular spectra obtained by photoassociation near a d-wave Feshbach resonance. This effect occurs due to quantum interference in PA transitions involving the continuum of atom-atom scattering states, the underlying Feshbach and photoassociated excited bound molecular states. We measure the variation in atom loss rate with an external magnetic field close to the Feshbach resonance in the presence of PA laser, and thereby clearly demonstrate the Fano effect. Our results further reveal that the Fano effect has significant influence on spectral shifts. Based on Fano's method, we develop a theory that explains the observed experimental results relatively well. Our theoretical formulation takes into account quantum interference between or among multiple transition pathways and between inelastic channels. Our results present a novel method for tuning the collisional interaction strength with laser light using Fano resonance.

Computational Probing of Watson-Crick/Hoogsteen Breathing in a DNA Duplex Containing N1-Methylated Adenine.

DNA breathing is a local conformational fluctuation spontaneously occurring in double-stranded DNAs. In particular, the possibility of individual base pairs (bps) in duplex DNA to flip between alternate bp modes, i.e., Watson-Crick (WC)-like and Hoogsteen (HG)-like, at relevant time scales has impacted DNA research fields for many years. In this study, to computationally probe effects of chemical modification on the DNA breathing, we present a free energy landscape of spontaneous thermal transitions between WC and HG bps in a free DNA duplex containing N1-methylated adenine (m1A). For the current free energy computation, a variant of well-tempered metadynamics simulation was extensively performed for a total of 40 μs to produce free energy surfaces. The free energy profile indicated that, upon the chemical modification of adenine, the HG bp (m1A·T) was located in the most favorable conformation (96.7%); however, the canonical WC bp (m1A·T) was distorted into two WC-like bps of WC* (2.8%) and WC** (0.5%). The conformational exchange between these two minor WC-like bps occurs with the first hundred nanoseconds. The transition between WC-like and HG bp features multiple transition pathways displaying various extents of base flipping in combination with glycosidic rotation. Analysis of the simulated ensemble showed that the m1A-induced changes of the backbone and sugar pucker were in a reasonable agreement with previous results inferred from NMR experiments. Also, this study revealed that the formation of the stable HG bp upon the mutation alters the characteristics of dynamic fluctuations of the neighboring WC residues of m1A. We expect this simulation approach to be a robust computational scheme to complement and guide future high-resolution experiments on many outstanding issues of duplex DNA breathing.

First-Principles Study of the α-β Phase Transition of Ferroelectric Poly(vinylidene difluoride): Observation of Multiple Transition Pathways.

Transition routes from the α (nonpolar) phase to the β (polar) phase of polyvinylidene difluoride (PVDF) are investigated by first-principles simulation methods. Among various possible routes, including complex torsional and rotational motions, we propose two prototypical transition routes and identify important intermediate structures along each transition pathway using the generalized solid-state nudged elastic band (G-SSNEB) method. The effect of the external electric field and mechanical drawing on the transition behavior is investigated by estimating electric enthalpy and stress tensors. Finite-temperature ab initio molecular dynamics (AIMD) simulations and stress tensor analysis reveal the possibility of enhancement of the crystallinity under hydrodynamic compression.

Protein-Ligand Interactions through the Computational Microscope: Allostery in a Canonical Signaling Domain

Protein-ligand interactions play a central role in many biological functions. These interactions modulate the dynamic conformational ensemble of a protein. By integrating long-timescale all-atom molecular dynamics simulations with Markov state models we have elucidate the conformational ensembles of PKA's cyclic-nucleotide binding domain A for the cAMP-free (apo) and cAMP-bound states. These models provide significant insight into the mechanisms of allostery in the cyclic-nucleotide binding domain. We show that the system exhibits a shallow free energy landscape that links functional states through multiple transition pathways, supporting conformational selection as the general mechanism of allostery in this canonical signaling domain. The models also illuminate the dynamic nature of protein-ligand interactions, show the transient nature of many of the key interactions between the cAMP and the cyclic-nucleotide binding domain.

Free energy landscape and transition pathways from Watson-Crick to Hoogsteen base pairing in free duplex DNA.

Houghton (HG) base pairing plays a central role in the DNA binding of proteins and small ligands. Probing detailed transition mechanism from Watson–Crick (WC) to HG base pair (bp) formation in duplex DNAs is of fundamental importance in terms of revealing intrinsic functions of double helical DNAs beyond their sequence determined functions. We investigated a free energy landscape of a free B-DNA with an adenosine–thymine (A–T) rich sequence to probe its conformational transition pathways from WC to HG base pairing. The free energy landscape was computed with a state-of-art two-dimensional umbrella molecular dynamics simulation at the all-atom level. The present simulation showed that in an isolated duplex DNA, the spontaneous transition from WC to HG bp takes place via multiple pathways. Notably, base flipping into the major and minor grooves was found to play an important role in forming these multiple transition pathways. This finding suggests that naked B-DNA under normal conditions has an inherent ability to form HG bps via spontaneous base opening events.

Allostery through the computational microscope: cAMP activation of a canonical signalling domain.

Ligand-induced protein allostery plays a central role in modulating cellular signaling pathways. Here, using the conserved cyclic-nucleotide binding domain of protein kinase A’s (PKA) regulatory subunit as a prototype signaling unit, we combine long-timescale, all-atom molecular dynamics simulations with Markov state models to elucidate the conformational ensembles of PKA’s cyclic-nucleotide binding domain A for the cAMP-free (apo) and cAMP-bound states. We find that both systems exhibit shallow free-energy landscapes that link functional states through multiple transition pathways. This observation suggests conformational selection as the general mechanism of allostery in this canonical signaling domain. Further, we expose the propagation of the allosteric signal through key structural motifs in the cyclic-nucleotide binding domain and explore the role of kinetics in its function. Our approach integrates disparate lines of experimental data into one cohesive framework to understand structure, dynamics, and function in complex biological systems.

Autonomous basin climbing method with sampling of multiple transition pathways: application to anisotropic diffusion of point defects in hcp Zr

This paper presents an extension of the autonomous basin climbing (ABC) method, an atomistic activation-relaxation technique for sampling transition-state pathways. The extended algorithm (ABC-E) allows the sampling of multiple transition pathways from a given minimum, with the additional feature of identifying the pathways in the order of increasing activation barriers, thereby prioritizing them according to their importance in the kinetics. Combined with on-the-fly kinetic Monte Carlo calculations, the method is applied to simulate the anisotropic diffusion of point defects in hcp Zr. Multiple migration mechanisms are identified for both the interstitials and vacancies, and benchmarked against results from other methods in the literature. The self-interstitial atom (SIA) diffusion kinetics shows a maximum anisotropy at intermediate temperatures (400~700 K), a non-monotonic behavior that we explain to originate from the stabilities and migration mechanisms associated with different SIA sites. The accuracy of the ABC-E calculations is validated, in part, by the existing results in the literature for point defect diffusion in hcp Zr, and by benchmarking against analytical results on a hypothetical rough-energy landscape. Lastly, sampling prioritization and computational efficiency are demonstrated through a direct comparison between the ABC-E and the activation relaxation technique.

Multiple pathways in conformational transitions of the alanine dipeptide: An application of dynamic importance sampling

We present multiple dynamic transition pathways on the two-dimensional dihedral plane between conformational states of the alanine dipeptide. The method used in this study is dynamic importance sampling (DIMS). To perform DIMS, unbiased molecular dynamic simulations are used to generate equilibrium ensembles for the alanine dipeptide within different states. Free energy surfaces on the dihedral plane are calculated from the equilibrium simulations, and four energy minima defined from the surface are used as the starting and ending points for DIMS dynamics. The DIMS method represents an important step towards finding multiple transition pathways within complex biomolecular systems.

Effects of physicochemical factors on the secondary structure of β-lactoglobulin

Fourier transform infrared spectroscopy and differential scanning calorimetry were used as complementary techniques to study changes in the secondary structure of beta-lactoglobulin under various physicochemical conditions. The effects of pH (3-9), NaCl (0-2 M), and lactose, glucose and sucrose (100-500 g/l) in the temperature range 25-100 degrees C on the conformation sensitive amide I band in the i.r. spectrum of beta-lactoglobulin in D2O solution were examined. The 1692 cm-1 band in the amide I band profile had not been definitively assigned in previous studies of the i.r. spectrum of beta-lactoglobulin. The decrease in this band at ambient temperature with time or upon mild heating was attributed to slow H-D exchange, indicating that it was due to a structure buried deep within the protein. The disappearance of the 1692 cm-1 band on heating was accompanied by the appearance of two bands at 1684 and 1629 cm-1, assigned to beta-sheets. The 1692 cm-1 band was therefore attributed to a beta-type structure. beta-Lactoglobulin showed maximum thermal stability at pH 3 and was easily denatured at pH 9. On denaturation, the protein unfolded into more extensive random coil structures at pH 9 than at pH 3. After 10 h at pH 9 (25 degrees C), beta-lactoglobulin was partly denatured. Heating to 60-80 degrees C generally resulted in the loss of secondary structure. At all pH values studied, two new bands at 1618 and 1684 cm-1, characteristic of intermolecular beta-sheet structure and associated with aggregation, were observed after the initial denaturation. Differential scanning calorimetry studies indicated that the thermal stability of beta-lactoglobulin was enhanced in the presence of sugars. The Fourier transform i.r. results obtained provide evidence that sugars promoted the unfolding of beta-lactoglobulin via multiple transition pathways leading to a transition state resisting aggregation.