Formation and dissociation of protonated cytosine–cytosine base pairs in i-motifs by ab initio quantum chemical calculations

Formation and dissociation mechanisms of C-C＋ base pairs in acidic and alkaline environments are investigated, employing ab initio quantum chemical calculations. Our calculations suggest that, in an acidic environment, a cytosine monomer is first protonated and then dimerized with an unprotonated cytosine monomer to form a C-C＋ base pair; in an alkaline environment, a protonated cytosine dimer is first unprotonated and then dissociated into two cytosine monomers. In addition, the force for detaching a C-C＋ base pair was found to be inversely proportional to the distance between the two cytosine monomers. These results provide a microscopic mechanism to qualitatively explain the experimentally observed reversible formation and dissociation of i-motifs.     

Diffusion-Limited Aggregation with Polygon Particles

Diffusion-limited aggregation (DLA) assumes that particles perform pure random walk at a finite temperature and aggregate when they come close enough and stick together. Although it is well known that DLA in two dimensions results in a ramified fractal structure, how the particle shape influences the formed morphology is still unclear. In this work, we perform the off-lattice two-dimensional DLA simulations with different particle shapes of triangle, quadrangle, pentagon, hexagon, and octagon, respectively, and compare with the results for circular particles. Our results indicate that different particle shapes only change the local structure, but have no effects on the global structure of the formed fractal cluster. The local compactness decreases as the number of polygon edges increases.     

Thermal properties of a two-dimensional intrinsically curved semiflexible biopolymer

We study the behaviors of mean end-to-end distance and specific heat of a two-dimensional intrinsically curved semiflexible biopolymer with a hard-core excluded volume interaction. We find the mean square end-to-end distance R~2_N∝ N~βat large N, with N being the number of monomers. Both β and proportional constant are dependent on the reduced bending rigidity κ and intrinsic curvature c. The larger the c, the smaller the proportional constant, and 1.5 ≥β≥ 1. Up to a moderate κ = κ_c, or down to a moderate temperature T = T_c, β = 1.5, the same as that of a self-avoiding random walk, and the larger the intrinsic curvature, the smaller the κ_c. However, at a large κ or a low temperature, β is close to 1,and the conformation of the biopolymer can be more compact than that of a random walk. There is an intermediate regime with 1.5 β 1 and the transition from β = 1.5 to β = 1 is smooth. The specific heat of the system increases smoothly with increasing κ or there is no peak in the specific heat. Therefore, a nonvanishing intrinsic curvature seriously affects the thermal properties of a semiflexible biopolymer, but there is no phase transition in the system.     

Modulation of intra- and inter-sheet interactions in short peptide self-assembly by acetonitrile in aqueous solution

Besides our previous experimental discovery(Zhao Y R, et al. 2015 Langmuir, 31, 12975) that acetonitrile(ACN)can tune the morphological features of nanostructures self-assembled by short peptides KIIIIK(KI4K) in aqueous solution,further experiments reported in this work demonstrate that ACN can also tune the mass of the self-assembled nanostructures.To understand the microscopic mechanism how ACN molecules interfere peptide self-assembly process, we conducted a series of molecular dynamics simulations on a monomer, a cross-β sheet structure, and a proto-fibril of KI4 K in pure water, pure ACN, and ACN-water mixtures, respectively. The simulation results indicate that ACN enhances the intra-sheet interaction dominated by the hydrogen bonding(H-bonding) interactions between peptide backbones, but weakens the inter-sheet interaction dominated by the interactions between hydrophobic side chains. Through analyzing the correlations between different groups of solvent and peptides and the solvent behaviors around the proto-fibril, we have found that both the polar and nonpolar groups of ACN play significant roles in causing the opposite effects on intermolecular interactions among peptides. The weaker correlation of the polar group of ACN than water molecule with the peptide backbone enhances H-bonding interactions between peptides in the proto-fibril. The stronger correlation of the nonpolar group of ACN than water molecule with the peptide side chain leads to the accumulation of ACN molecules around the proto-fibril with their hydrophilic groups exposed to water, which in turn allows more water molecules close to the proto-fibril surface and weakens the inter-sheet interactions. The two opposite effects caused by ACN form a microscopic mechanism clearly explaining our experimental observations.     

Folding nucleus and unfolding dynamics of protein 2GB1

The folding of many small proteins is kinetically a two-state process with one major free-energy barrier to overcome,which can be roughly regarded as the inverse process of unfolding.In this work,we first use a Gaussian network model to predict the folding nucleus corresponding to the major free-energy barrier of protein 2 GB1,and find that the folding nucleus is located in theβ-sheet domain.High-temperature molecular dynamics simulations are then used to investigate the unfolding process of 2 GB1.We draw free-energy surface from unfolding simulations,taking RMSD and contact number as reaction coordinates,which confirms that the folding of 2 GB1 is kinetically a two-state process.The comparison of the contact maps before and after the free energy barrier indicates that the transition from native to non-native structure of the protein is kinetically caused by the destruction of theβ-sheet domain,which manifests that the folding nucleus is indeed located in theβ-sheet domain.Moreover,the constrained MD simulation further confirms that the destruction of the secondary structures does not alter the topology of the protein retained by the folding nucleus.These results provide vital information for upcoming researchers to further understand protein folding in similar systems.     

Anisotropic formation mechanism and nanomechanics for the self-assembly process of cross-β peptides

Nanostructures self-assembled by cross-β peptides with ordered structures and advantageous mechanical properties have many potential applications in biomaterials and nanotechnologies. Quantifying the intra-and inter-molecular driving forces for peptide self-assembly at the atomistic level is essential for understanding the formation mechanism and nanomechanics of various morphologies of self-assembled peptides. We investigate the thermodynamics of the intra-and inter-sheet structure formations in the self-assembly process of cross-β peptide KIIIIK by means of steered molecular dynamics simulation combined with umbrella sampling. It is found that the mechanical properties of the intra-and inter-sheet structures are highly anisotropic with their intermolecular bond stiffness at the temperature of 300 K being 5.58 N/m and0.32 N/m, respectively. This mechanical anisotropy comes from the fact that the intra-sheet structure is stabilized by enthalpy but the inter-sheet structure is stabilized by entropy. Moreover, the formation process of KIIIIK intra-sheet structure is cooperatively driven by the van der Waals(VDW) interaction between the hydrophobic side chains and the electrostatic interaction between the hydrophilic backbones, but that of the inter-sheet structure is primarily driven by the VDW interaction between the hydrophobic side chains. Although only peptide KIIIIK is studied, the qualitative conclusions on the formation mechanism should also apply to other cross-β peptides.     

Moderate point: Balanced entropy and enthalpy contributions in soft matter

Various soft materials share some common features, such as significant entropic effect, large fluctuations, sensitivity to thermodynamic conditions, and mesoscopic characteristic spatial and temporal scales. However, no quantitative definitions have yet been provided for soft matter, and the intrinsic mechanisms leading to their common features are unclear. In this work, from the viewpoint of statistical mechanics, we show that soft matter works in the vicinity of a specific thermodynamic state named moderate point, at which entropy and enthalpy contributions among substates along a certain order parameter are well balanced or have a minimal difference. Around the moderate point, the order parameter fluctuation,the associated response function, and the spatial correlation length maximize, which explains the large fluctuation, the sensitivity to thermodynamic conditions, and mesoscopic spatial and temporal scales of soft matter, respectively. Possible applications to switching chemical bonds or allosteric biomachines determining their best working temperatures are also briefly discussed.