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

J. Appl. Cryst.の発刊に際して

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.

For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.

Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

/pdf/guidelines-for-the-use-and-interpretation-of-assays-for-ijf2t30pbq.pdf

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

/pdf/guidelines-for-the-use-and-interpretation-of-assays-for-28d1pi1jvo.pdf

Guidelines for the use and interpretation of assays for monitoring autophagy

Selectively 2H- and 13C-labeled spermines (SPM) were efficiently synthesized and analyzed by NMR spectroscopy to determine the spin–spin coupling constants for six conformationally relevant bonds. SPM that is composed of three alkyl moieties, a butanylene, and two propanylene chains undergoes a conformational change when interacting with multivalent anions (e.g., adenosine triphosphate (ATP), ATP–Mg2+, and tripolyphosphate). Upon interaction with ATP, the CC bonds, which affect the distance between the neighboring pairs of ammonium groups (i.e., N1/N5 and N5/N5′), increase the population of gauche rotamers by 17–20 % relative to those in the 4 HCl salt of SPM. However, the trend in increments of the gauche conformers for the SPM–ATP complex profoundly differs from that of the spermidine (SPD)–ATP complex. This implies that SPM may preferentially recognize the adenyl group of ATP rather than the tripolyphosphate moiety. This may account for the higher affinity of SPM to ATP–Mg2+ than with that of SPD, which chiefly interacts with β- and γ-phosphates and is easily replaced by Mg2+. These results may provide a clue for the further understanding of the structural basis of polyamine biological functions.

Conformations of spermine in adenosine triphosphate complex: the structural basis for weak bimolecular interactions of major cellular electrolytes.

β-Glucosylation of cholesterol reduces sterol-sphingomyelin interactions

Structural diversity and molecular flexibility of phospholipids are essential for biological membranes to play key roles in numerous cellular processes. Uncovering the behavior of individual lipids in membrane dynamics is crucial for understanding the molecular mechanisms underlying biological functions of cell membranes. In this paper, we introduce a simple method to investigate dynamics of lipid molecules in multi-component systems by measuring the (31) P chemical shift anisotropy (CSA) under magic angle spinning (MAS) conditions. For achieving both signal separation and CSA determination, we utilized a centerband-only analysis of rotor-unsynchronized spin echo (COARSE). This analysis is based on the curve fitting of periodic modulation of centerband intensity along the interpulse delay time in rotor-unsynchronized spin-echo experiments. The utility of COARSE was examined by using phospholipid vesicles, a three-component lipid raft model system, and archaeal purple membranes. We found that the apparent advantages of this method are high resolution and high sensitivity given by the moderate MAS speed and the one-dimensional acquisition with short spin-echo delays. COARSE provides an alternative method for CSA measurement that is effective in the investigation of lipid polymorphologies.

Centerband-only analysis of rotor-unsynchronized spin echo for measurement of lipid (31) P chemical shift anisotropy.

/pdf/derivatization-and-isotope-labeling-of-amphotericin-b-aiming-2w1ouxjjeo.pdf

Derivatization and Isotope Labeling of Amphotericin B Aiming at Elucidation of the Ion-channel Structure

The present invention relates to the compound A of the formula (A), the related compound B, carboxylic acid derived from acid anhydride group of these compounds and esters and salts thereof, microorganisms for producing the compounds, methods for producing the compounds A and/or B by using the microorganisms, and a treated or untreated fermentation broth obtained by culturing strains belonging to genus Zopfiella or Zopfiella curvata No. 37-3 strain. ##STR1## The present invention provides the compounds A and B, derivatives thereof, and treated or untreated fermentation broth obtained by culturing the strains belonging to genus Zopfiella or Zopfiella curvata No. 37-3 strain, which show an excellent activities as antifungal agent and anti-thrombotic agent.

Michio Murata

Papers

Conformations of spermine in adenosine triphosphate complex: the structural basis for weak bimolecular interactions of major cellular electrolytes.

β-Glucosylation of cholesterol reduces sterol-sphingomyelin interactions

Centerband-only analysis of rotor-unsynchronized spin echo for measurement of lipid (31) P chemical shift anisotropy.

Derivatization and Isotope Labeling of Amphotericin B Aiming at Elucidation of the Ion-channel Structure

Fermentation broth and microorganisms which produce them