Dynamics of water confined in the interdomain region of a multidomain protein

Molecular dynamics simulations are performed to study the dynamics of interfacial water confined in the interdomain region of a two-domain protein, BphC enzyme. The results show that near the protein surface the water diffusion constant is much smaller and the water-water hydrogen bond lifetime is much longer than that in bulk. The diffusion constant and hydrogen bond lifetime can vary by a factor of as much as 2 in going from the region near the hydrophobic domain surface to the bulk. Water molecules in the first solvation shell persist for a much longer time near local concave sites than near convex sites. Also, the water layer survival correlation time shows that on average water molecules near the extended hydrophilic surfaces have longer residence times than those near hydrophobic surfaces. These results indicate that local surface curvature and hydrophobicity have a significant influence on water dynamics.     

Numerical Simulation of Anisotropy Directions in Soft Tissues and in Particular in Skin

Orientation of collagen fibers and their spatial distribution predefine macroscopic mechanical properties of the soft tissue and in particular its anisotropy directions. In this contribution, we apply two different procedures to automatically generate these directions for a 3D FE-model. The first procedure is based on an analogy with a heat conduction problem. Accordingly, a thermal flux under certain temperature boundary conditions is calculated by the same FE model and is further utilized for the definition of the anisotropy directions. The numerical result shows good agreement with Langer's lines data in human skin. Within the second procedure, the fiber vector field is calculated by the Laplacian smoothing method based on the user defined fiber direction sketches. (© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Tuning the In Vivo Transport of Anticancer Drugs Using Renal‐Clearable Gold Nanoparticles

Precise control of in vivo transport of anticancer drugs in normal and cancerous tissues with engineered nanoparticles is key to the future success of cancer nanomedicines in clinics. This requires a fundamental understanding of how engineered nanoparticles impact the targeting‐clearance and permeation‐retention paradoxes in the anticancer‐drug delivery. Herein, we systematically investigated how renal‐clearable gold nanoparticles (AuNPs) affect the permeation, distribution, and retention of the anticancer drug doxorubicin in both cancerous and normal tissues. Renal‐clearable AuNPs retain the advantages of the free drug, including rapid tumor targeting and high tumor vascular permeability. The renal‐clearable AuNPs also accelerated body clearance of off‐target drug via renal elimination. These results clearly indicate that diverse in vivo transport behaviors of engineered nanoparticles can be used to reconcile long‐standing paradoxes in the anticancer drug delivery.     

Aggregation‐Induced‐Emission‐Active Macrocycle Exhibiting Analogous Triply and Singly Twisted Möbius Topologies

Molecules with Möbius topology have drawn increasing attention from scientists in a variety of fields, such as organic chemistry, inorganic chemistry, and material science. However, synthetic difficulties and the lack of functionality impede their fundamental understanding and practical applications. Here, we report the facile synthesis of an aggregation‐induced‐emission (AIE)‐active macrocycle (TPE‐ET) and investigate its analogous triply and singly twisted Möbius topologies. Because of the twisted and flexible nature of the tetraphenylethene units, the macrocycle adjusts its conformations so as to accommodate different guest molecules in its crystals. Moreover, theoretical studies including topological and electronic calculations reveal the energetically favorable interconversion process between triply and singly twisted topologies.     

Limit for the Euler-genus distributions of ladder-like sequences of graphs

Journal of Algebraic Combinatorics - In this paper, we demonstrate a method for calculating the production matrices for the Euler-genus polynomials of H-linear families of graphs. Particularly, for...     

Clustering Algorithms to Analyze Molecular Dynamics Simulation Trajectories for Complex Chemical and Biological Systems?

Molecular dynamics (MD) simulation has become a powerful tool to investigate the structurefunction relationship of proteins and other biological macromolecules at atomic resolution and biologically relevant timescales. MD simulations often produce massive datasets containing millions of snapshots describing proteins in motion. Therefore, clustering algorithms have been in high demand to be developed and applied to classify these MD snapshots and gain biological insights. There mainly exist two categories of clustering algorithms that aim to group protein conformations into clusters based on the similarity of their shape (geometric clustering) and kinetics (kinetic clustering). In this paper, we review a series of frequently used clustering algorithms applied in MD simulations, including divisive algorithms, agglomerative algorithms (single-linkage, complete-linkage, average-linkage, centroid-linkage and ward-linkage), center-based algorithms (K-Means, K-Medoids, K-Centers, and APM), density-based algorithms (neighbor-based, DBSCAN, density-peaks, and Robust-DB), and spectral-based algorithms (PCCA and PCCA+). In particular, differences between geometric and kinetic clustering metrics will be discussed along with the performances of different clustering algorithms. We note that there does not exist a one-size-fits-all algorithm in the classification of MD datasets. For a specific application, the right choice of clustering algorithm should be based on the purpose of clustering, and the intrinsic properties of the MD conformational ensembles. Therefore, a main focus of our review is to describe the merits and limitations of each clustering algorithm. We expect that this review would be helpful to guide researchers to choose appropriate clustering algorithms for their own MD datasets.     

Convergence of folding free energy landscapes via application of enhanced sampling methods in a distributed computing environment

We have implemented the serial replica exchange method (SREM) and simulated tempering (ST) enhanced sampling algorithms in a global distributed computing environment. Here we examine the helix-coil transition of a 21 residue alpha-helical peptide in explicit solvent. For ST, we demonstrate the efficacy of a new method for determining initial weights allowing the system to perform a random walk in temperature space based on short trial simulations. These weights are updated throughout the production simulation by an adaptive weighting method. We give a detailed comparison of SREM, ST, as well as standard MD and find that SREM and ST give equivalent results in reasonable agreement with experimental data. In addition, we find that both enhanced sampling methods are much more efficient than standard MD simulations. The melting temperature of the Fs peptide with the AMBER99phi potential was calculated to be about 310 K, which is in reasonable agreement with the experimental value of 334 K. We also discuss other temperature dependent properties of the helix-coil transition. Although ST has certain advantages over SREM, both SREM and ST are shown to be powerful methods via distributed computing and will be applied extensively in future studies of complex bimolecular systems.     

弯曲型Lamb波传播特性与固井质量相关性研究

轻质水泥在油田固井中的广泛应用使得传统测井方式无法有效的对固井水泥胶结质量做出评价。为了研究新的可行的评价方法,本文采用传递矩阵方法对套管中传播的弯曲型Lamb波进行建模,并通过对所建模型进行数值计算研究了套管外水泥等介质的声学参数变化对弯曲型Lamb波衰减率的影响。数值计算的结果表明,弯曲型Lamb波的衰减率与水泥的声学参数以及水泥与套管的胶结状况有较强相关性,据此可对水泥与套管胶结状况进行评价。本文的计算结果与分析对弯曲型Lamb波在水泥胶结评价中的应用具有一定的参考意义。     

Changes in microbial community structure and function within particle size fractions of a paddy soil under different long-term fertilization treatments from the Tai Lake region, China

Greenhouse gas (GHG) production and emission from paddy soils impacts global climate change. Soil particle size fractions (PSFs) of different sizes act as soil microhabitats for different kinds of microbial biota with varying conditions of redox reactions and soil organic matter (SOC) substrates. It is crucial to understand the distribution of soil microbial community structure within PSFs and linkage to the GHG production from paddy soils of China. The change of bacterial and methangenic archaeal community and activity relating to CH₄ and CO₂ production with PSFs under different fertilizer applications was studied in this paper. The fertilization trial was initiated in a paddy soil from the Tai Lake region, Jiangsu, China with four treatments of non-fertilized (NF), fertilized with inorganic fertilizers only (CF), inorganic with pig manure (CFM) and inorganic with straw return (CFS), respectively since 1987, and the PSFs (<2 μm, 2–20 μm, 20–200 μm, and 200–2000 μm) were separated by a low energy sonication dispersion procedure from undisturbed samples. Analysis of bacterial community within different size particles was conducted by PCR-DGGE. The results indicated significant variation of bacterial community structure within different PSFs. The methane was predominantly produced in the coarser fractions, while more species and higher diversity of bacteria survived in the size of <2 μm fractions, in which the bacterial community structure was more significantly affected by fertilizer application practices than in the other coarser fractions. Higher bacterial species richness and more diversities in the smallest size fractions was due to the vicinity between microbes, access to carbon resource outside the microaggregates, and smaller pore size as protective agent suitable habitats for microbes rather than high SOC. Whereas, higher CO₂, CH₄ production and methanogenic archaeal community in coarser fractions may be contributed to storage of labile organic carbon in these fractions. It indicated that availability of SOC in PSFs is mainly factor affected survival of methanogenic archaeal community structure, whereas, bacterium community habitation more affected by physical protection of their location in PSFs. Their activity greatly depended on liability of SOC access to PSFs. Fertilizer application caused more change of bacteria community in clay fraction and greatly increased bacterium and methanogen activity in coarser fractions but only a slight effect on methanogenic archaeal community in the particle size fractions.     

Renal Clearable Luminescent WSe2 for Radioprotection of Nontargeted Tissues during Radiotherapy

High‐energy ionizing radiation is widely used in medical diagnosis and cancer radiation therapy. However, high‐energy radiation can also impose significant damages in healthy tissues during medical treatments via direct DNA damages and indirect damages from production of reactive oxygen species (ROS). Therefore, it is urgent to develop highly effective radioprotectants with low toxicities that can meet the increasing needs for alleviating the adverse effects from cancer radiation therapy and nuclear emergency. In this work, strongly catalytic ultrasmall (sub‐5 nm) cysteine‐protected WSe₂ dots are employed to protect healthy tissues against radiation via diminishing radiation‐induced free radicals. The WSe₂ dots with high surface activities can recover radiation‐induced DNA damages and eliminate the excessive ROS generated from radiation. In vivo experiments confirm that the survival rate of mice treated with WSe₂ dots is significantly elevated with radiation damages postponed under exposure to high‐dose ionizing radiation. Furthermore, the free radicals in major organs and hematological system can be appreciably omitted, suggesting their unique role as free radical scavengers. These WSe₂ dots in ultrasmall size show rapid renal clearance of ≈74% injection dose via urine excretion in 24 h and do not cause any apparent toxicity in vivo for up to 30 d.