Thermodynamic Insights of Base Flipping in TNA Duplex: Force Fields, Salt Concentrations, and Free-Energy Simulation Methods

Threofuranosyl nucleic acid(TNA)is an analogue of DNA with a shift in the internucleotide linkages from the wild-type 5’-to-3’direction to 3’-to-2.’This alteration leads to higher chemical stability,less reactive groups,and lower conformational flexibility.Experimental observations indicate that these characteristic changes are attributable to a minimal perturbation of the interaction network,but the thermodynamic stability of the duplex remains unaltered in the TNA mutation.We applied the equilibrium and nonequilibrium free-energy simulations employing three popular assisted model building with energy refinement(AMBER)force fields for nucleotides to investigate this mutation-dependent behavior in the base flipping from T(DNA)residue to the T-to-TFT mutation(TNA)computationally.The force fields were performed similarly,as described in the base-paired state.However,after exploring the high-energy regions with free-energy simulations,we observed that these three force fields behaved differently.Previous reports conclude that the net-neutral and excess-salt simulations provided similar results.Nonetheless,our free-energy simulation indicated that the presence of excess salt affected the thermodynamic stability.The free-energy barrier along the base-flipping pathway was generally elevated upon the addition of excess salts,but the relative height of the free-energy barriers in DNA and TNA duplexes did not change significantly.This phenomenon emphasizes the importance of adding sufficient salts in the simulation scheme to reproduce the experimental condition.

Nonequilibrium thermodynamics and fluctuation relations for small systems

In this review, we give a retrospect of the recent progress in nonequilibrium statistical mechanics and thermodynamics in small dynamical systems. For systems with only a few number of particles, fluctuations and nonlinearity become sig- nificant and contribute to the nonequilibrium behaviors of the systems, hence the statistical properties and thermodynamics should be carefully studied. We review recent developments of this topic by starting from the Gallavotti-Cohen fluctuation theorem, and then to the Evans-Searles transient fluctuation theorem, Jarzynski free-energy equality, and the Crooks fluc- tuation relation. We also investigate the nonequilibrium free energy theorem for trajectories involving changes of the heat bath temperature and propose a generalized free-energy relation. It should be noticed that the non-Markovian property of the heat bath may lead to the violation of the free-energy relation.

Critical Finite Size Scaling Relation of the Order-Parameter Probability Distribution for the Three-Dimensional Ising Model on the Creutz Cellular Automaton

We study the order parameter probability distribution at the critical point for the three-dimensional spin-1/2 and spin-1 Ising models on the simple cubic lattice under periodic boundary conditions. The finite size scaling relation for the order parameter probability distribution is tested and verified numerically by microcanonical Creutz cellular automata simulations. The state critical exponent δ, which characterizes the far tail regime of the scaling order parameter probability distribution, is estimated for three-dimensional Ising models using the cellular automaton simulations at the critical temperature. The results are in good agreement with the Monte Carlo calculations.

Distribution of Equilibrium Free Energies in a Thermodynamic System with Broken Ergodicity

At low temperatures the configurational phase space of a macroscopic complex system （e.g., a spin-glass） of N - 10^23 interacting particles may split into an exponential number Ωs - exp（const × N） of ergodic sub-spaces （thermodynamic states）. It is usually assumed that the equilibrium collective behavior of such a system is determined by its ground thermodynamic states of the minimal free-energy density, and that the equilibrium free energies follow the distribution of exponentied decay. But actually for some complex systems, the equilibrium free-energy values may follow a Gaussian distribution within an intermediate temperature range, and consequently their equilibrium properties are contributed by excited thermodynamic states. Based on this analysis, the re-weighting parameter y in the cavity approach of spin-glasses is easily understood. Depending on the free-energy distribution, the optimal y can either be equal to or be strictly less than the inverse temperature β.

Topological Defects in Liquid Crystal Films

A topological theory of liquid crystal films in the presence of defects is developed based on the Ф-mapping topological current theory. By generalizing the free-energy density in ＂one-constant＂ approximation, a covariant free- energy density is obtained, from which the U（1） gauge field and the unified topological current for monopoles and strings in liquid crystals are derived. The inner topological structure of these topological defects is characterized by the winding numbers of Ф-mapping.

Structural and thermodynamic properties of inhomogeneous fluids in rectangular corrugated nano-pores

Based on the free-energy average method,an area-weighted effective potential is derived for rectangular corrugated nano-pore.With the obtained potential,classical density functional theory is employed to investigate the structural and thermodynamic properties of confined Lennard-Jones fluid in rectangular corrugated slit pores.Firstly,influence of pore geometry on the adsorptive potential is calculated and analyzed.Further,thermodynamic properties including excess adsorption,solvation force,surface free energy and thermodynamic response functions are systematically investigated.It is found that pore geometry can largely modulate the structure of the confined fluids,which in turn influences other thermodynamic properties.In addition,the results show that different geometric elements have different influences on the confined fluids.The work provides an effective route to investigate the effect of roughness on confined fluids.It is expected to shed light on further understanding about interfacial phenomena near rough walls,and then provide useful clues for the design and characterization of novel materials.

Numerical Simulation of Muzzle Flow Field Based on Calculation of Combustion Productions in Bore

To improve the accuracy of numerical simulation of muzzle chemical flow field,and study the gunpowder combustion productions, the muzzle flow field is simulated coupled with the calculation of combustion productions in bore. The calculation in bore uses the gibbs free-energy minimization method and the classical interior ballistics model. The simulation of the muzzle flow field employs the multi-component ALE( Arbitrary Lagrange-Euler) equations. Computations are performed for a 12. 7 mm gun. From 2. 48 ms to3. 14 ms,the projectile moves in the gun barrel. CO and H2 O masses decrease by 3. 37% and 6. 51%,and H2 and CO2masses increase by 11. 11% and 10. 58%. The changes conform to the fact that the water-gas equilibrium reaction of all reactions plays a dominant role in this phase. After the projectile leaves the barrel,the masses of H2 and CO decrease,and the masses of H2 O and CO2 increase. When it moves to 80 d away from the muzzle,the decreases are 12. 75% and 8. 05%,and the increases are 12. 76% and 36. 26%,which tallies with the existence of muzzle flame. Further,CO and H2 burn more and more fiercely with the muzzle pressure pg increasing,and burn more and more weakly with the altitude rising. When two projectiles launch in series,the combustion of the second projectile muzzle flow field is fiercer than the first projectile. Analysis results have shown that the proposed method is effective for simulating the muzzle flow filed.

Biophysical Mechanism of the SAHA Inhibition of Zn^（2+）-Histone Deacetylase-Like Protein(FB188 HDAH)Assessed via Crystal Structure Analysis

The zinc-containing enzyme HDAC-like amidohydrolase (FB188 HDAH), identified in the Bordetella alcaligenes bacteria, is similar to enzymes that participate in epigenetic mechanisms such as histone modifications. The X-ray crystal structure of FB188 HDAH complexed with the antagonist SAHA (suberoylanilide hydroxamic acid) has been solved (PDB ID: 1ZZ1). Notably, the complex crystallizes as a tetramer in the asymmetric unit cell of the crystal. The crystal yielded a suitable structure to analyze the dynamics of the inhibitory mechanism of SAHA on this histone deacetylase. Applying computational chemistry techniques and quantum mechanics theory, several physicochemical properties were calculated to compare the active site of the enzyme of the four monomers. Significant differences were observed in the areas and volumes of the binding pocket, as well as hydrophobic interactions, dipole moments, atomic charges and electrostatic potential, among other properties. Remarkably, a free-energy curve resulting from the evaluation of the energies of SAHA and the interacting amino acids of the four crystal monomers unveiled the biophysical mechanism of the FB188 HDAH inhibition exerted by SAHA to a greater extent. The biophysical mechanism of SAHA inhibition on FB188 deacetylase was clearly observed as a dynamic process. It is possible to define the physicochemical dynamics of the molecular complex by the application of computational chemistry techniques and quantum mechanics theory by studying the crystal structures of the interacting molecules.

Design of artificial biomimetic channels with Na^(+)permeation rate and selectivity potentially outperforming the natural sodium channel

Artificial ion channels that enable high-efficiency ion transport have important implications in nanofluidics and biomedical applications such as drug delivery.Herein,we show a simulation-based chemical design of a biomimetic sodium channel that possesses permeation rate and selectivity potentially higher than those of the state-of-the-art natural vertebrate voltage-gated sodium channels.Importantly,our theoretical findings have undergone empirical testing,aligning well with the Arrhenius law as derived from a diverse range of experimental results.The high-efficiency ion transport is achieved by anchoring the carboxylate functional groups within the channel filter.A key chemical guiding principle underlying the ion channel design is that the free-energy barrier for the Na^(+)passage across the channel should be comparable to typical thermal energy at room temperature.With the implementation of the chemical design,we found that the relatively low free-energy barrier can be attributed to the compensation effect of the carboxylate groups to the partially lost oxygen shell of the ion within the ion channel,as well as to the consonant vibration of the ions inside and outside the channel.This mechanistic understanding brings new insight,at the molecular level,into the high-efficiency ion transport across the designed membrane channels.The proof of principle achieved from the simulations will stimulate future experimental confirmation and potential applications of the high-performance artificial channels in nanofluidics and in bioinspired iontronics.