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

We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1 megabase. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.

/pdf/comprehensive-mapping-of-long-range-interactions-reveals-15wp5ww9ic.pdf

Comprehensive mapping of long-range interactions reveals folding principles of the human genome.

http://experimentationlab.berkeley.edu/sites/default/files/AFMImages/butt_AFM.pdf

Force measurements with the atomic force microscope: Technique, interpretation and applications

A nanopore-based device provides single-molecule detection and analytical capabilities that are achieved by electrophoretically driving molecules in solution through a nano-scale pore. The nanopore provides a highly confined space within which single nucleic acid polymers can be analyzed at high throughput by one of a variety of means, and the perfect processivity that can be enforced in a narrow pore ensures that the native order of the nucleobases in a polynucleotide is reflected in the sequence of signals that is detected. Kilobase length polymers (single-stranded genomic DNA or RNA) or small molecules (e.g., nucleosides) can be identified and characterized without amplification or labeling, a unique analytical capability that makes inexpensive, rapid DNA sequencing a possibility. Further research and development to overcome current challenges to nanopore identification of each successive nucleotide in a DNA strand offers the prospect of 'third generation' instruments that will sequence a diploid mammalian genome for ∼$1,000 in ∼24 h.

/pdf/the-potential-and-challenges-of-nanopore-sequencing-51qxscif85.pdf

The Potential and Challenges of Nanopore Sequencing

Solid-state nanopores are sensors capable of analysing individual unlabelled DNA molecules in solution. Although the critical information obtained from nanopores (for example, DNA sequence) comes from the signal collected during DNA translocation, the throughput of the method is determined by the rate at which molecules arrive and thread into the pores. Here, we study the process of DNA capture into nanofabricated SiN pores of molecular dimensions. For fixed analyte concentrations we find an increase in capture rate as the DNA length increases from 800 to 8,000 base pairs, a length-independent capture rate for longer molecules, and increasing capture rates when ionic gradients are established across the pore. Furthermore, we show that application of a 20-fold salt gradient allows the detection of picomolar DNA concentrations at high throughput. The salt gradients enhance the electric field, focusing more molecules into the pore, thereby advancing the possibility of analysing unamplified DNA samples using nanopores.

Electrostatic focusing of unlabelled DNA into nanoscale pores using a salt gradient

We present measurements and theoretical modeling of the ionic conductance G of solid-state nanopores with 5-100 nm diameters, with and without DNA inserted into the pore. First, we show that it is essential to include access resistance to describe the conductance, in particular for larger pore diameters. We then present an exact solution for G of an hourglass-shaped pore, which agrees very well with our measurements without any adjustable parameters, and which is an improvement over the cylindrical approximation. Subsequently we discuss the conductance blockade ΔG due to the insertion of a DNA molecule into the pore, which we study experimentally as a function of pore diameter. We find that ΔG decreases with pore diameter, contrary to the predictions of earlier models that forecasted a constant ΔG. We compare three models for ΔG, all of which provide good agreement with our experimental data.

https://iopscience.iop.org/article/10.1088/0957-4484/22/31/315101/pdf

Modeling the conductance and DNA blockade of solid-state nanopores.

Measurements on protein translocation through solid-state nanopores reveal anomalous (non-Smoluchowski) transport behavior, as evidenced by extremely low detected event rates; that is, the capture rates are orders of magnitude smaller than what is theoretically expected. Systematic experimental measurements of the event rate dependence on the diffusion constant are performed by translocating proteins ranging in size from 6 to 660 kDa. The discrepancy is observed to be significantly larger for smaller proteins, which move faster and have a lower signal-to-noise ratio. This is further confirmed by measuring the event rate dependence on the pore size and concentration for a large 540 kDa protein and a small 37 kDa protein, where only the large protein follows the expected behavior. We dismiss various possible causes for this phenomenon and conclude that it is due to a combination of the limited temporal resolution and low signal-to-noise ratio. A one-dimensional first-passage time-distribution model supports...

Fast Translocation of Proteins through Solid State Nanopores

http://www.rowland.harvard.edu/labs/meller/BJ_3205.pdf

Nanopore Unzipping of Individual DNA Hairpin Molecules

We argue that in order to maintain the biological function of DNA confined inside the cell nucleus, its spatial structure has to be unknotted, of the so-called crumpled globule type. The fixation of a particular realization of this non-equilibrium structure by attractive interactions between specific units imposes a connection between the spatial structure of DNA and the statistical distribution of these units along the chain contour. This suggests that both primary sequence and spatial structure of native DNA were formed simultaneously by a self-similar evolution process. The predictions of our model are compared with recent observations of long-range correlations in intron-containing genes and non-transcribed regulatory elements and further experimental tests are proposed.

http://iopscience.iop.org/article/10.1209/0295-5075/23/5/012/pdf

Yitzhak Rabin

Papers

Electrostatic focusing of unlabelled DNA into nanoscale pores using a salt gradient

Modeling the conductance and DNA blockade of solid-state nanopores.

Fast Translocation of Proteins through Solid State Nanopores

Nanopore Unzipping of Individual DNA Hairpin Molecules

Crumpled globule model of the three-dimensional structure of DNA