Simulating ion channel activation mechanisms using swarms of trajectories

Atomic-level studies of protein activity represent a significant challenge as a result of the complexity of conformational changes occurring on wide-ranging timescales, often greatly exceeding that of even the longest simulations. A prime example is the elucidation of protein allosteric mechanisms, where localized perturbations transmit throughout a large macromolecule to generate a response signal. For example, the conversion of chemical to electrical signals during synaptic neurotransmission in the brain is achieved by specialized membrane proteins called pentameric ligand-gated ion channels. Here, the binding of a neurotransmitter results in a global conformational change to open an ion-conducting pore across the nerve cell membrane. X-ray crystallography has produced static structures of the open and closed states of the proton-gated GLIC pentameric ligand-gated ion channel protein, allowing for atomistic simulations that can uncover changes related to activation. We discuss a range of enhanced sampling approaches that could be used to explore activation mechanisms. In particular, we describe recent application of an atomistic string method, based on Roux's “swarms of trajectories” approach, to elucidate the sequence and interdependence of conformational changes during activation. We illustrate how this can be combined with transition analysis and Brownian dynamics to extract thermodynamic and kinetic information, leading to understanding of what controls ion channel function. © 2019 Wiley Periodicals, Inc.     

金属串配合物[MoMoCo(npo)4(NCS)2]的配位结构及其与电场的关系

应用密度泛函理论B3LYP方法研究了具有分子导线潜在应用的金属串配合物[MoMoCo(npo)4(NCS)2](npo=1,8-萘基-2-酮)的配位结构及其受电场作用的影响。配位方式记为(n,m),其中n、m分别表示4个赤道配体npo^-的O与Co和Mo配位的个数:n=0,1,2,3,4;m=4,3,2,1,0。结果表明:(1)零电场下,基态能量高低为(0,4)>(4,0)>(3,1)≈(1,3)>(2,2),5种配位方式均可稳定存在且互为竞争态。Z方向偶极矩μ(Z)值大小为(0,4)(+)>(1,3)(+)>(2,2)(-)>(3,1)(-)>(4,0)(-)(+、-表示μ(Z)值的正负,与Z方向相同即为正,相反即为负),4个npo^-趋向越一致能量越高极性越大。(2)Mo-Mo具有四重键,键长随μ(Z)值减小而减小,而Mo-Co键长则相反。随μ(Z)值减小前线轨道中πNCS(1)轨道能降低,π'NCS(2)轨道能升高。(3)Z方向电场作用下,除(0,4)外所有配位方式的Mo1-N8键显著增长,结构不稳定。(4)电场作用下前线轨道能级交错,μ(Z)为正值的(0,4)、(1,3)的能隙E_LUMO-HOMO在-Z方向电场中降低更显著,μ(Z)为负值的(2,2)、(3,1)和(4,0)的能隙在Z方向电场中降低更显著。分子极性越大,随电场强度增强能隙降低越显著,分子导电性可能越好。(0,4)、(3,1)和(4,0)可能具有整流效应,但(3,1)和(4,0)的稳定性较低。     

Note about Hamiltonian dynamics of string in non-relativistic D3-brane background

This paper is devoted to the study of the Hamiltonian dynamics of string in non-relativistic D3-brane background. We discuss different gauge fixing functions and construct corresponding gauge fixed Hamiltonians.     

Intranuclear-Cascade model calculation of photofission probabilities for actinide nuclei

We have calculated the fission probabilities for ²³⁷Np, ^{233, 235, 238}U, ²³²Th, and ^natPb following the absorption of photons with energies from 68 MeV to 3.77 GeV using the RELDIS Monte Carlo code. This code implements the cascade-evaporation-fission model of intermediate-energy photonuclear reactions. It includes multiparticle production in photoreactions on intranuclear nucleons, pre-equilibrium emission, and the statistical decay of excited residual nuclei via competition of evaporation, fission, and multifragmentation processes. The calculations show that in the GeV energy region the fission process is not solely responsible for the entire total photoabsorption cross-section, even for the actinides. The fission probabilities are 80-95% for ²³³U, ²³⁵U, and ²³⁷Np, 70-80% for ²³⁸U, and only 55-70% for ²³²Th. This is because certain residual nuclei that are created by deep photospallation at GeV photon energies have relatively low fission probabilities. The results of those model calculations are in reasonable agreement (at the 10% level) with recent experimental data on relative photofission cross-sections for ²³⁷Np and ^{233, 235, 238}U (but not for ²³²Th or ^natPb) from the Saskatchewan and Jefferson Laboratories over a very wide range in photon energy. Using our calculated fission probabilities plus the total photoabsorption cross-sections per nucleon, estimated from previous cross-section data for nuclei from C to Pb, we can infer absolute photofission cross-sections for the actinide nuclei and compare them with the SAL and JLab results. The resulting discrepancies, however, clearly demonstrate the need for direct measurement of the total photoabsorption cross-sections for the heavy actinides.     

Non-Static Local String in Higher-Dimensional Gravity

We analyze the space-time structure of local gauge string with a phenomenological energy–momentum tensor, as prescribed by Vilenkin, in an arbitrary number of space-time dimensions with a non-zero cosmological constant Λ. A set of solutions of the full non-linear Einstein's equations for the interior region of such a string is presented.     

A stabilization law for two semi-infinite interacting strings of characters

We consider a Markov chain that describes the evolution of two interacting strings of symbols. The transitions probalitities of this Markov chain depend only on the rightmost symbols of both strings. The main goal of the present paper is to prove a limit theorem (stabilization law): the distribution of the rightmost symbols converges to some limit correlation function.1 Partially supported by FAPESP (2002/01501-9) and RFBR (02-01-00415)2 Partially supported by RFBR (02-01-00415)     

Accelerating Flat Universe and Analytic Study of the m-z Relation

An accelerating flat universe with a variable cosmological term is obtained in the Robertson-Walker metric. The variable cosmological term is defined by the correction terms of the metric tensor field. Simple solutions of the scale factor and the cosmological term are shown. In this model of the universe, the magnitude-redshift relation is analytically studied to see if the model reproduces the tendency of the present observational data. The equation of state parameter is touched.     

Hadron spectroscopy and structure from AdS/CFT

The AdS/CFT correspondence between conformal field theory and string states in an extended space-time has provided new insights into not only hadron spectra, but also their light-front wave functions. We show that there is an exact correspondence between the fifth-dimensional coordinate of anti-de Sitter space z and a specific impact variable ζ which measures the separation of the constituents within the hadron in ordinary space-time. This connection allows one to predict the form of the light-front wave functions of mesons and baryons, the fundamental entities which encode hadron properties and scattering amplitudes. A new relativistic Schr?dinger light-front equation is found which reproduces the results obtained using the fifth-dimensional theory. Since they are complete and orthonormal, the AdS/CFT model wave functions can be used as an initial ansatz for a variational treatment or as a basis for the diagonalization of the light-front QCD Hamiltonian. A number of applications of light-front wave functions are also discussed.     

Stable bundle extensions on elliptic Calabi–Yau threefolds

We construct stable bundle extensions on elliptically fibered Calabi–Yau threefolds. We show that these bundles can solve the topological anomaly constraint in heterotic string theory without the need for invoking background five-branes.