Maximum Flux Transition Paths of Conformational Change

Given two metastable states A and B of a biomolecular system, the problem is to calculate the likely paths of the transition from A to B. Such a calculation is more informative and more manageable if done for a reduced set of collective variables chosen so that paths cluster in collective variable space. The computational task becomes that of computing the "center" of such a cluster. A good way to define the center employs the concept of a committor, whose value at a point in collective variable space is the probability that a trajectory at that point will reach B before A. The committor "foliates" the transition region into a set of isocommittors. The maximum flux transition path is defined as a path that crosses each isocommittor at a point which (locally) has the highest crossing rate of distinct reactive trajectories. (This path is different from that of the MaxFlux method of Huo and Straub.) It is argued that such a path is nearer to an ideal path than others that have been proposed with the possible exception of the finite-temperature string method path. To make the calculation tractable, three approximations are introduced, yielding a path that is the solution of a nonsingular two-point boundary-value problem. For such a problem, one can construct a simple and robust algorithm. One such algorithm and its performance is discussed.Comment: 7 figure

String Method for the Study of Rare Events

We present a new and efficient method for computing the transition pathways, free energy barriers, and transition rates in complex systems with relatively smooth energy landscapes. The method proceeds by evolving strings, i.e. smooth curves with intrinsic parametrization whose dynamics takes them to the most probable transition path between two metastable regions in the configuration space. Free energy barriers and transition rates can then be determined by standard umbrella sampling technique around the string. Applications to Lennard-Jones cluster rearrangement and thermally induced switching of a magnetic film are presented.Comment: 4 pages, 4 figure

Spurious diffusion in particle simulations of the Kolmogorov flow

Particle simulations of the Kolmogorov flow are analyzed by the Landau-Lifshitz fluctuating hydrodynamics. It is shown that a spurious diffusion of the center of mass corrupts the statistical properties of the flow. The analytical expression for the corresponding diffusion coefficient is derived.Comment: 10 pages, no figure

Problematic social media use in childhood and adolescence.

At the time of writing, about 4.59 billion people use social media with many adolescents using their social media accounts across a myriad of applications and platforms. According to recent statistics, in 2022 individuals spent an average of 151 minutes on social media each day, illustrating the global relevance of social media (Dixon, 2022a,b). One of the pressing questions, internationally, is whether social media use is harmful and/or addictive. This question is of particular importance because many teenagers - and younger adolescents - spend considerable time on these platforms, which have increasingly become an integral part of their lives. Moreover, considering lifespan development, adolescents may be particularly vulnerable to specific features and advertisements shown to them on social media platforms. Growing prevalence of poor mental health in young people has led to recent recommendations in the United States to routinely screen for anxiety in 8-18 year olds, and for depression and suicide risk for adolescents between 12-18 years of age (US Preventive Services Task Force et al., 2022 a,b) - the conditions often accompanying problematic social media use. The present work not only provides insights into the current state of the literature but provides also recommendations. [Abstract copyright: Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Classical motion in force fields with short range correlations

We study the long time motion of fast particles moving through time-dependent random force fields with correlations that decay rapidly in space, but not necessarily in time. The time dependence of the averaged kinetic energy and mean-squared displacement is shown to exhibit a large degree of universality; it depends only on whether the force is, or is not, a gradient vector field. When it is, p^{2}(t) ~ t^{2/5} independently of the details of the potential and of the space dimension. Motion is then superballistic in one dimension, with q^{2}(t) ~ t^{12/5}, and ballistic in higher dimensions, with q^{2}(t) ~ t^{2}. These predictions are supported by numerical results in one and two dimensions. For force fields not obtained from a potential field, the power laws are different: p^{2}(t) ~ t^{2/3} and q^{2}(t) ~ t^{8/3} in all dimensions d\geq 1

Structure Determination of Oligosaccharides Isolated from A + , H + and A − H − Hog-Submaxillary-Gland Mucin Glyoproteins, by 360-MHz 1 H-NMR Spectroscopy, Permethylation Analysis and Mass Spectrometry

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65915/1/j.1432-1033.1981.tb05545.x.pd

Optimisation of ITER Nb3Sn CICCs for coupling loss, transverse electromagnetic load and axial thermal contraction

The ITER cable-in-conduit conductors (CICCs) are built up from sub-cable bundles, wound in different stages, which are twisted to counter coupling loss caused by time-changing external magnet fields. The selection of the twist pitch lengths has major implications for the performance of the cable in the case of strain sensitive superconductors, i.e. Nb3Sn, as the electromagnetic and thermal contraction loads are large but also for the heat load from the AC coupling loss. Reduction of the transverse load and warm-up cool-down degradation can be reached by applying longer twist pitches in a particular sequence for the sub-stages, offering a large cable transverse stiffness, adequate axial flexibility and maximum allowed lateral strand support. Analysis of short sample (TF conductor) data reveals that increasing the twist pitch can lead to a gain of the effective axial compressive strain of more than 0.3 % with practically no degradation from bending. For reduction of the coupling loss, specific choices of the cabling twist sequence are needed with the aim to minimize the area of linked strands and bundles that are coupled and form loops with the applied changing magnetic field, instead of simply avoiding longer pitches. In addition we recommend increasing the wrap coverage of the CS conductor from 50 % to at least 70 %. The models predict significant improvement against strain sensitivity and substantial decrease of the AC coupling loss in Nb3Sn CICCs, but also for NbTi CICCs minimization of the coupling loss can be achieved. Although the success of long pitches to transverse load degradation was already demonstrated, the prediction of the combination with low coupling loss needs to be validated by a short sample test.Comment: to be published in Supercond Sci Techno

Minimum Free Energy Path of Ligand-Induced Transition in Adenylate Kinase

Large-scale conformational changes in proteins involve barrier-crossing transitions on the complex free energy surfaces of high-dimensional space. Such rare events cannot be efficiently captured by conventional molecular dynamics simulations. Here we show that, by combining the on-the-fly string method and the multi-state Bennett acceptance ratio (MBAR) method, the free energy profile of a conformational transition pathway in Escherichia coli adenylate kinase can be characterized in a high-dimensional space. The minimum free energy paths of the conformational transitions in adenylate kinase were explored by the on-the-fly string method in 20-dimensional space spanned by the 20 largest-amplitude principal modes, and the free energy and various kinds of average physical quantities along the pathways were successfully evaluated by the MBAR method. The influence of ligand binding on the pathways was characterized in terms of rigid-body motions of the lid-shaped ATP-binding domain (LID) and the AMP-binding (AMPbd) domains. It was found that the LID domain was able to partially close without the ligand, while the closure of the AMPbd domain required the ligand binding. The transition state ensemble of the ligand bound form was identified as those structures characterized by highly specific binding of the ligand to the AMPbd domain, and was validated by unrestrained MD simulations. It was also found that complete closure of the LID domain required the dehydration of solvents around the P-loop. These findings suggest that the interplay of the two different types of domain motion is an essential feature in the conformational transition of the enzyme