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

다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

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

Molecular simulation is an extremely useful, but computationally very expensive tool for studies of chemical and biomolecular systems Here, we present a new implementation of our molecular simulation toolkit GROMACS which now both achieves extremely high performance on single processors from algorithmic optimizations and hand-coded routines and simultaneously scales very well on parallel machines The code encompasses a minimal-communication domain decomposition algorithm, full dynamic load balancing, a state-of-the-art parallel constraint solver, and efficient virtual site algorithms that allow removal of hydrogen atom degrees of freedom to enable integration time steps up to 5 fs for atomistic simulations also in parallel To improve the scaling properties of the common particle mesh Ewald electrostatics algorithms, we have in addition used a Multiple-Program, Multiple-Data approach, with separate node domains responsible for direct and reciprocal space interactions Not only does this combination of a

/pdf/gromacs-4-algorithms-for-highly-efficient-load-balanced-and-16xnd83poh.pdf

GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation

New developments in the science of learning science of learning overview mind and brain how experts differ from novices how children learn learning and transfer the learning environment curriculum, instruction and commnity effective teaching - examples in history, mathematics and science teacher learning technology to support learning conclusions from new developments in the science of learning.

How people learn: Brain, mind, experience, and school.

A series of novel, multisubstrate, bicyclic pyrimidine nucleoside inhibitors of human thymidine phosphorylase (TP) is described. Thymidine phosphorylase has been implicated in angiogenesis and plays a significant role in tumor progression and metastasis. The presence and orientation of the phosphonate moiety (acting as a phosphate mimic) in these derivatives were critical for inhibitory activity. The most active compounds possessed a phosphonate group in an endo orientation. This was consistent with molecular modeling results that showed the endo isomer protein-ligand complex to be lower in energy than the exo complex.

Synthesis and evaluation of multisubstrate bicyclic pyrimidine nucleoside inhibitors of human thymidine phosphorylase.

Algorithms are described and analyzed for the efficient evaluation of the primitive operators of a relational algebra on a proposed non-von Neumann machine based on a hierarchy of associative storage devices. This architecture permits an O(log n) decrease in time complexity over the best known evaluation methods on a conventional computer system, without the use of redundant storage, and using currently available and potentially competitive technology. In many eases of practical import, the proposed architecture may also permit a significant improvement (by a factor roughly proportional to the capacity of the primary associative storage device) over the performance of previously implemented or proposed database machine architectures based on associative secondary storage devices.

/pdf/a-hierarchical-associative-architecture-for-the-parallel-4jd44v0srb.pdf

A hierarchical associative architecture for the parallel evaluation of relational algebraic database primitives

Exploiting parallelism to accelerate a computation typically involves dividing it into many small tasks that can be assigned to different processing elements. An efficient execution schedule for these tasks can be difficult or impossible to determine in advance, however, if there is uncertainty as to when each task's input data will be available. Ideally, each task would run in direct response to the arrival of its input data, thus allowing the computation to proceed in a fine-grained event-driven manner. Realizing this ideal is difficult in practice, and typically requires sacrificing flexibility for performance.In Anton 2, a massively parallel special-purpose supercomputer for molecular dynamics simulations, we addressed this challenge by including a hardware block, called the dispatch unit, that provides flexible and efficient support for fine-grained event-driven computation. Its novel features include a many-to-many mapping from input data to a set of synchronization counters, and the ability to prioritize tasks based on their type. To solve the additional problem of using a fixed set of synchronization counters to track input data for a potentially large number of tasks, we created a software library that allows programmers to treat Anton 2 as an idealized machine with infinitely many synchronization counters. The dispatch unit, together with this library, made it possible to simplify our molecular dynamics software by expressing it as a collection of independent tasks, and the resulting fine-grained execution schedule improved overall performance by up to 16% relative to a coarse-grained schedule for precisely the same computation.

Hardware support for fine-grained event-driven computation in Anton 2

SIMD and MSIMD Variants of the NON-VON Supercomputer.

The SARS-CoV-2 nonstructural proteins coordinate genome replication and gene expression. Structural analyses revealed the basis for coupling of the essential nsp13 helicase with the RNA-dependent RNA polymerase (RdRp) where the holo-RdRp and RNA substrate (the replication-transcription complex or RTC) associated with two copies of nsp13 (nsp132-RTC). One copy of nsp13 interacts with the template-RNA in an opposing polarity to the RdRp and is envisaged to drive the RdRp backward on the RNA template (backtracking), prompting questions as to how the RdRp can efficiently synthesize RNA in the presence of nsp13. Here we use cryogenic-electron microscopy and molecular dynamics simulations to analyze the nsp132-RTC, revealing four distinct conformational states of the helicases. The results indicate a mechanism for the nsp132-RTC to turn backtracking on and off, using an allosteric mechanism to switch between RNA synthesis or backtracking in response to stimuli at the RdRp active site. 

/pdf/ensemble-cryo-em-reveals-conformational-states-of-the-nsp13-1kq0n29d.pdf

David E. Shaw

Papers

Synthesis and evaluation of multisubstrate bicyclic pyrimidine nucleoside inhibitors of human thymidine phosphorylase.

A hierarchical associative architecture for the parallel evaluation of relational algebraic database primitives

Hardware support for fine-grained event-driven computation in Anton 2

SIMD and MSIMD Variants of the NON-VON Supercomputer.

Ensemble cryo-EM reveals conformational states of the nsp13 helicase in the SARS-CoV-2 helicase replication–transcription complex