Biomolecular Simulation: A Perspective from High Performance Computing

High-Performance Computing is impacting on all biomedical sciences, including molecular biophysics. Here, we describe general parallel computing strategies (multi-threading and distributed computing) used in all the natural sciences, including molecular biophysics. Next, we describe how these strategies are applied in molecular dynamics simulations and enhanced sampling methods, either based on force fields, on density functional theory or on QM/MM potentials. As test cases, we focus on the widely used CPMD and GROMACS packages, along with a hybrid QM/MM interface coupling the two recently developed by a European team including the Authors. The review closes with a short perspective on the use of HPC-based biomolecular simulations. Additional information on optimizations and software adjustments to maximize code performance are provided in the Supporting Information.     

Scanning ion conductance microscopy: a convergent high-resolution technology for multi-parametric analysis of living cardiovascular cells

Cardiovascular diseases are complex pathologies that include alterations of various cell functions at the levels of intact tissue, single cells and subcellular signalling compartments. Conventional techniques to study these processes are extremely divergent and rely on a combination of individual methods, which usually provide spatially and temporally limited information on single parameters of interest. This review describes scanning ion conductance microscopy (SICM) as a novel versatile technique capable of simultaneously reporting various structural and functional parameters at nanometre resolution in living cardiovascular cells at the level of the whole tissue, single cells and at the subcellular level, to investigate the mechanisms of cardiovascular disease. SICM is a multimodal imaging technology that allows concurrent and dynamic analysis of membrane morphology and various functional parameters (cell volume, membrane potentials, cellular contraction, single ion-channel currents and some parameters of intracellular signalling) in intact living cardiovascular cells and tissues with nanometre resolution at different levels of organization (tissue, cellular and subcellular levels). Using this technique, we showed that at the tissue level, cell orientation in the inner and outer aortic arch distinguishes atheroprone and atheroprotected regions. At the cellular level, heart failure leads to a pronounced loss of T-tubules in cardiac myocytes accompanied by a reduction in Z-groove ratio. We also demonstrated the capability of SICM to measure the entire cell volume as an index of cellular hypertrophy. This method can be further combined with fluorescence to simultaneously measure cardiomyocyte contraction and intracellular calcium transients or to map subcellular localization of membrane receptors coupled to cyclic adenosine monophosphate production. The SICM pipette can be used for patch-clamp recordings of membrane potential and single channel currents. In conclusion, SICM provides a highly informative multimodal imaging platform for functional analysis of the mechanisms of cardiovascular diseases, which should facilitate identification of novel therapeutic strategies.     

Lithium technologies for edge plasma control

We have investigated two new modes of operation been in T-10 limiter tokamak experiments with a novel rotary feeder of lithium dust. Quasi steady-state mode I and pulse mode II of dust delivery were realized in both OH and OH + ECRH disruption free plasmas at the lithium flow rate up to 2 × 10²¹ atoms/s. A higher flow rate in mode II with injection rate of ～5 × 10²¹ atoms/s caused a series of minor disruptions, which was completed by discharge termination after the major disruption. The observed decreases of bolometer and D_β signals, with increase of the electron density during the lithium dust injection, reveal the effects of the first wall conditioning. The lithium technology may provide inherent safety pathway for major disruption mitigation in a tokamak reactor, which requires demonstration in contemporary tokamak experiments.     

微棱镜逆反射材料特性分析及制作

对微棱镜逆反射材料进行了理论研究和实验制作.理论分析了微棱镜单元内光线的逆反射特性,并研究了全反射条件对入射孔径角的限制以及阵列结构的逆反射率.提出了一种新的工艺方法,用于制作大尺寸的微棱镜模版.该方法将小尺寸镍模版利用类似"盖章"的方法在较大尺寸的聚碳酸酯基底上依次压制并使其紧密排列,然后再利用电铸的方法生长出大尺寸镍工作模版.最终得到了尺寸为500 mm×100 mm的模版.使用其制作的样片的逆反射系数最高大于750 cd/(1x·m2).     

Fatty Acid,Lipid Class,and Phospholipid Molecular Species Composition of the Soft Coral Xenia sp. (Nha Trang Bay,the South China Sea,Vietnam)

The soft corals of the genus Xenia are common for Indo‐Pacific reef ecosystems. Lipid class, fatty acid (FA), phospho‐ and phosphonolipid molecular species compositions were identified for the first time in the soft coral Xenia sp. from Vietnam. Total lipids consisted predominantly of waxes, monoalkyl diacylglycerols, triacylglycerols, sterols, and polar lipids (21.4, 7.7, 14.2, 10.5, and 36.7 %, respectively). Sesquiterpene alcohol, valerenenol, was found. Acids 16:0, 18:3n‐6, 20:4n‐6, and 20:5n‐3 dominated in total FA. The markers of zooxanthellae (18:4n‐3 and 18:5n‐3) and octocorals (24:5n‐6 and 24:6n‐3) were detected. Acids 18:5n‐3, 20:4n‐6, 22:4n‐6, and 24:5n‐6 concentrated in FA of polar lipids, whereas 14:0, 16:0, 16:1n‐7, 18:2n‐6, and 18:3n‐6 were the major FA of neutral lipids. ChoGpl, EtnGpl, SerGpl, CAEP, PtdIns, and lyso ChoGpl constituted 39.5, 20.8, 20.5, 9.7, 4.3, and 5.3 %, respectively, of the sum of phospho‐ and phosphonolipids. Thirty‐two molecular species of phospholipids and ceramide aminoethylphosphonate (CAEP) were determined by high resolution tandem mass spectrometry. Lyso 18:0e PakCho (4.1 %), 18:0e/20:4 PakCho (20.5 %), 18:1e/20:4 PlsEtn (18.0 %), 18:0e/24:5 PakSer (14.0 %), and 16:0 CAEP (9.6 %) were the major molecular species. EtnGpl and PtdIns mainly consisted of alkenyl acyl and diacyl forms, respectively. Alkyl acyl forms predominated in ChoGpl and SerGpl. Acid 24:5n‐6 was a principal FA in SerGpl, whereas 20:4n‐6 was more abundant in ChoGpl and EtnGpl. PtdIns contained various C_20–24 PUFA. In the context of chemotaxonomy of corals, Xenia sp. has the lipid composition typical for soft corals and the FA profile similar to that of alcyonarians with the high level of 18:3n‐6.     

The Effect of Duration of Amidation of Fatty Acids with Diethanolamine on the Surfactant Properties

The effects of the duration of direct amidation of fatty acids (FA) with diethanolamine on the composition of the products obtained, their surface-active properties, and ability to stabilize water-in-oil emulsions are studied using the example of tall oil distillate. A certain range of synthesis time that corresponds to the maximum content of diethanolamides in the reaction products, and, as a consequence, the highest surface-active and emulsifying properties of the products is shown to exist. An increase in the synthesis duration time leads to a deterioration of these properties due to accumulation of the products of secondary reactions. A new mechanism of the amidation process that includes secondary transformations of diethanolamine and its condensation products with FA into 1,4-bis(2-hydroxyethyl)piperazine derivatives is proposed. The structures of by-products are confirmed using high-performance liquid chromatography-mass spectrometry (HPLC–MS), infrared (IR), and nuclear magnetic resonance (NMR) spectroscopy methods. It is concluded that the acid value of the product as well as the amount of water released during the synthesis cannot serve as a reliable criterion for completion of the process.     

Unusual Reaction of N-Arylimines of Hexafluoroacetone with m-Chloroperoxybenzoic Acid. New Route to 2,2-Bis(trifluoromethyl)benzoxazolidines

Reaction of readily available N-arylimines of hexafluoroacetone with anhydrous m-chloroperoxybenzoic acid leads to the formation of substituted 2,2-bis(trifluoromethyl)oxazolidines in 30–70% yield as a result of an oxidative cyclization reaction. This process is general and can be used as a synthetic route to the corresponding polyfluorinated oxazolidines.     

Mechanical investigation of weak regions in a wound oxide-oxide ceramic matrix composite

The main aim of the investigation was to quantify the influence of production-related cross-lines on static mechanical properties (tensile, flexural and shear) of an oxide-oxide CMC as a comparison between specimens with cross-lines and specimens without cross-lines in tested regions. Investigated material was a weak-matrix oxide-oxide CMC (WHIPOX?) made of Nextel? 610 fibers (3000 denier) and alumina matrix with a special winding pattern. Mechanical tests at room temperature revealed that cross-lines were local weak regions in a wound component. Spatial separation of the cross-line within the composite (2?mm shift from layer to layer) did not improve the negative influence of the cross-lines on mechanical properties. Fractographic investigations revealed that cross-lines acted as a trigger of material failure.