Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a fixed subset of atoms; the second assigns each a fixed subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently—those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 100,000,000 atoms on several parallel supercomputers--the nCUBE 2, Intel iPSC/860 and Paragon, and Cray T3D. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and a 1840-node Intel Paragon performs up to 165 faster than a single Cray C9O processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.

Fast parallel algorithms for short-range molecular dynamics

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

1. Introduction 20642. Synthesis of Magnetic Nanoparticles 20662.1. Classical Synthesis by Coprecipitation 20662.2. Reactions in Constrained Environments 20682.3. Hydrothermal and High-TemperatureReactions20692.4. Sol-Gel Reactions 20702.5. Polyol Methods 20712.6. Flow Injection Syntheses 20712.7. Electrochemical Methods 20712.8. Aerosol/Vapor Methods 20712.9. Sonolysis 20723. Stabilization of Magnetic Particles 20723.1. Monomeric Stabilizers 20723.1.1. Carboxylates 20733.1.2. Phosphates 20733.2. Inorganic Materials 20733.2.1. Silica 20733.2.2. Gold 20743.3. Polymer Stabilizers 20743.3.1. Dextran 20743.3.2. Polyethylene Glycol (PEG) 20753.3.3. Polyvinyl Alcohol (PVA) 20753.3.4. Alginate 20753.3.5. Chitosan 20753.3.6. Other Polymers 20753.4. Other Strategies for Stabilization 20764. Methods of Vectorization of the Particles 20765. Structural and Physicochemical Characterization 20785.1. Size, Polydispersity, Shape, and SurfaceCharacterization20795.2. Structure of Ferro- or FerrimagneticNanoparticles20805.2.1. Ferro- and Ferrimagnetic Nanoparticles 20805.3. Use of Nanoparticles as Contrast Agents forMRI20825.3.1. High Anisotropy Model 20845.3.2. Small Crystal and Low Anisotropy EnergyLimit20855.3.3. Practical Interests of Magnetic NuclearRelaxation for the Characterization ofSuperparamagnetic Colloid20855.3.4. Relaxation of Agglomerated Systems 20856. Applications 20866.1. MRI: Cellular Labeling, Molecular Imaging(Inﬂammation, Apoptose, etc.)20866.2.

Magnetic Iron Oxide Nanoparticles: Synthesis, Stabilization, Vectorization, Physicochemical Characterizations, and Biological Applications

The endoplasmic reticulum (ER) responds to the accumulation of unfolded proteins in its lumen (ER stress) by activating intracellular signal transduction pathways - cumulatively called the unfolded protein response (UPR). Together, at least three mechanistically distinct arms of the UPR regulate the expression of numerous genes that function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids and lipids. The arms of the UPR are integrated to provide a response that remodels the secretory apparatus and aligns cellular physiology to the demands imposed by ER stress.

Signal integration in the endoplasmic reticulum unfolded protein response

https://easyspin.org/pubs/easyspin_jmr06.pdf

EasySpin, a comprehensive software package for spectral simulation and analysis in EPR.

An analysis of dynamical aspects of the CIDEP mechanism proposed by Wong et al. is given. This mechanism is based upon the formation of an excited triplet by intersystem crossing that populates the three triplet levels unequally. The subsequent rotational averaging of the initial population distribution coupled with the orientational effects of the zero field splitting is carefully treated in this work utilizing the stochastic Liouville equation in a manner closely analogous to that recently given for ESR line shapes and relaxation of slow−tumbling triplets. It is shown that the predicted CIDEP polarizations can indeed be very substantial, in agreement with Wong et al., but they will depend in general on the relative magnitudes of not only the zero field (D and E) and Zeeman terms (ω0) but also the relevant reaction rates and the rotational tumbling times (τR). A useful perturbation expression valid for D2 ≲ (1/2)[ω02 + τR−2] is obtained which shows these details. Typical complete solutions, obtained nume...

Theory of chemically induced dynamic electron polarization. III. Initial triplet polarizations

Structure-Function Studies Link Class II Viral Fusogens with the Ancestral Gamete Fusion Protein HAP2.

An analysis of aspects of the theory of chemically induced dynamic nuclear polarization (CIDNP) is given in terms of rigorous numerical solutions to the stochastic Liouville equation, in accordance with the methods previously developed for CIDEP. This analysis includes not only a model in which the exchange interaction is of finite extent in the spin Hamiltonian (EFA model) but models in which the exchange interaction explicitly affects the reactive trajectories (EFP model) by their inclusion in a spin‐dependent diffusion equation and in which charge interactions between reacting ionic radicals and their surroundings are accounted for in the Debye‐Huckel fashion. Several useful and simple relationships are found for the CIDNP phenomenon, and their dependence upon the model is discussed. It is found that the CIDNP polarizations are readily described in terms of two fundamental parameters‐Λ, the spin‐independent probability of reaction of singlets per collision, which includes all re‐encounters, and F*, which measures the conversion from triplets to singlets for the whole collision. Exact relations for the CIDNP polarizations are given in terms of these two parameters and are found to be nearly independent of model. The parameter Λ is shown to be simply related to k(r), the singlet reaction rate when the radicals are in contact, and to τ1, the effective lifetime of the reacting pair. Simple expressions for τ1 are given for all the models, and these results are compared with those for the usual discussions of diffusion rates on chemical kinetics. It is found that for normal diffusion rates, F* obeys the relation (1/2)Qτd, very similar to that first proposed by Adrian, where Q is half the difference in resonant frequencies of the radicals, and τd =d2/D with D the relative diffusion coefficient and d the distance of closest approach. This relation is not appropriate for viscous systems, and the correct results are given for such cases. The effects of the finite range of the exchange interaction and the longer range Coulombic interactions between radicals upon F* for the different models are also obtained. In particular, for EFA the finite range of exchange yields an ``excluded volume'' effect wherein singlet‐triplet mixing (or Q mixing) is ineffective. The model dependent effects upon F* are closely related to the recurrence probabilities, and further results are obtained implying a simple expression for the first encounter probabilities of separated radicals under the effects of the different interactions. The polarizations are related to the time‐dependent CIDNP intensities that one may observe for a typical scheme of radical production, reaction, and relaxation.

Erratum: Some theoretical aspects of chemically-induced dynamic nuclear polarization

Amyloid fibrils are cross-β–rich aggregates that are exceptionally stable forms of protein assembly. Accumulation of tau amyloid fibrils is involved in many neurodegenerative diseases, including Alzheimer’s disease (AD). Heparin-induced aggregates have been widely used and assumed to be a good tau amyloid fibril model for most biophysical studies. Here we show that mature fibrils made of 4R tau variants, prepared with heparin or RNA, spontaneously depolymerize and release monomers when their cofactors are removed. We demonstrate that the cross-β-sheet assembly formed in vitro with polyanion addition is unstable at room temperature. We furthermore demonstrate high seeding capacity with transgenic AD mouse brain-extracted tau fibrils in vitro that, however, is exhausted after one generation, while supplementation with RNA cofactors resulted in sustained seeding over multiple generations. We suggest that tau fibrils formed in brains are supported by unknown cofactors and inhere higher-quality packing, as reflected in a more distinct conformational arrangement in the mouse fibril-seeded, compared with heparin-induced, tau fibrils. Our study suggests that the role of cofactors in tauopathies is a worthy focus of future studies, as they may be viable targets for diagnosis and therapeutics.

https://www.pnas.org/content/pnas/115/52/13234.full.pdf

Cofactors are essential constituents of stable and seeding-active tau fibrils

Electron spin resonance (ESR) spectra were obtained at 250 and 9 GHz for nitroxide-labeled mutants of the protein T4 lysozyme in aqueous solution over a range of temperatures from 2 to 37.5 °C. Two mutants labeled at sites 72 and 131 were studied and compared. The mutant sites are solvent exposed and free of tertiary interactions with other side chains, but the former is at the center of a 5 turn helix, whereas the latter site is on a small two and a half turn helix. The 250 GHz ESR spectra, because of their “fast time scale”, are rather insensitive to the slow overall tumbling motion of the protein. Thus, they are qualitatively different for the two mutants, implying that there are different local dynamics at the two sites. The 9 GHz spectra, which are significantly affected by the overall tumbling and are less sensitive to the internal dynamics, do not show such marked differences between the two sites. The 250 and 9 GHz spectra for each mutant and temperature were simultaneously fit to the slowly relax...

https://www.acert.cornell.edu/PDFs/JPhysChemB108_17649_2004.pdf

Jack H. Freed

Papers

Theory of chemically induced dynamic electron polarization. III. Initial triplet polarizations

Structure-Function Studies Link Class II Viral Fusogens with the Ancestral Gamete Fusion Protein HAP2.

Erratum: Some theoretical aspects of chemically-induced dynamic nuclear polarization

Cofactors are essential constituents of stable and seeding-active tau fibrils

A multifrequency electron spin resonance study of T4 lysozyme dynamics using the slowly relaxing local structure model