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

Computational geometry

Image processing pipelines combine the challenges of stencil computations and stream programs. They are composed of large graphs of different stencil stages, as well as complex reductions, and stages with global or data-dependent access patterns. Because of their complex structure, the performance difference between a naive implementation of a pipeline and an optimized one is often an order of magnitude. Efficient implementations require optimization of both parallelism and locality, but due to the nature of stencils, there is a fundamental tension between parallelism, locality, and introducing redundant recomputation of shared values.We present a systematic model of the tradeoff space fundamental to stencil pipelines, a schedule representation which describes concrete points in this space for each stage in an image processing pipeline, and an optimizing compiler for the Halide image processing language that synthesizes high performance implementations from a Halide algorithm and a schedule. Combining this compiler with stochastic search over the space of schedules enables terse, composable programs to achieve state-of-the-art performance on a wide range of real image processing pipelines, and across different hardware architectures, including multicores with SIMD, and heterogeneous CPU+GPU execution. From simple Halide programs written in a few hours, we demonstrate performance up to 5x faster than hand-tuned C, intrinsics, and CUDA implementations optimized by experts over weeks or months, for image processing applications beyond the reach of past automatic compilers.

Halide: a language and compiler for optimizing parallelism, locality, and recomputation in image processing pipelines

Molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) and molecular mechanics generalized Born surface area (MM/GBSA) are arguably very popular methods for binding free energy prediction since they are more accurate than most scoring functions of molecular docking and less computationally demanding than alchemical free energy methods. MM/PBSA and MM/GBSA have been widely used in biomolecular studies such as protein folding, protein-ligand binding, protein-protein interaction, etc. In this review, methods to adjust the polar solvation energy and to improve the performance of MM/PBSA and MM/GBSA calculations are reviewed and discussed. The latest applications of MM/GBSA and MM/PBSA in drug design are also presented. This review intends to provide readers with guidance for practically applying MM/PBSA and MM/GBSA in drug design and related research fields.

End-Point Binding Free Energy Calculation with MM/PBSA and MM/GBSA: Strategies and Applications in Drug Design

Molecular docking methodology explores the behavior of small molecules in the binding site of a target protein. As more protein structures are determined experimentally using X-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy, molecular docking is increasingly used as a tool in drug discovery. Docking against homology-modeled targets also becomes possible for proteins whose structures are not known. With the docking strategies, the druggability of the compounds and their specificity against a particular target can be calculated for further lead optimization processes. Molecular docking programs perform a search algorithm in which the conformation of the ligand is evaluated recursively until the convergence to the minimum energy is reached. Finally, an affinity scoring function, ΔG [U total in kcal/mol], is employed to rank the candidate poses as the sum of the electrostatic and van der Waals energies. The driving forces for these specific interactions in biological systems aim toward complementarities between the shape and electrostatics of the binding site surfaces and the ligand or substrate.

Software for molecular docking: a review

Standard cache-oblivious recursive divide-and-conquer algorithms for evaluating dynamic programming recurrences have optimal serial cache complexity but often have lower parallelism compared with iterative wavefront algorithms due to artificial dependencies among subtasks. Very recently cache-oblivious recursive wavefront (COW) algorithms have been introduced which do not have any artificial dependencies. Though COW algorithms are based on fork-join primitives, they extensively use atomic operations, and as a result, performance guarantees provided by state-of-the-art schedulers for programs with fork-join primitives do not apply. In this work, we show how to systematically transform standard cache-oblivious recursive divide-and-conquer algorithms into recursive wavefront algorithms to achieve optimal parallel cache complexity and high parallelism under state-of-the-art schedulers for fork-join programs. Unlike COW algorithms these new algorithms do not use atomic operations. Instead, they use closed-form formulas to compute at what time each recursive function must be launched in order to achieve high parallelism without losing cache performance. The resulting implementations are arguably much simpler than implementations of known COW algorithms.

https://dl.acm.org/doi/pdf/10.1145/3018743.3019031

POSTER: Provably Efficient Scheduling of Cache-Oblivious Wavefront Algorithms

Stencil computations are widely used to simulate the change of state of physical systems. The current best algorithm for performing aperiodic linear stencil computations on a d (≥ 1)-dimensional grid of size N for T timesteps does Θ(TN1-1/d+N Log N) work. We introduce novel techniques based on random walks and Gaussian approximations for an asymptotic improvement of this work bound for a class of linear stencils. We also improve the span (i.e., parallel running time on an unbounded number of processors) asymptotically from the current state of the art.

Brief Announcement: Faster Stencil Computations using Gaussian Approximations

https://academic.oup.com/comjnl/advance-article-pdf/doi/10.1093/comjnl/bxab181/41161267/bxab181.pdf

A Unified Framework to Discover Permutation Generation Algorithms

Dynamic Programming (DP) provides optimal solutions to a problem by combining optimal solutions to many overlapping subproblems. DP algorithms exploit this overlapping property to explore otherwise exponential-sized problem spaces in polynomial time, making them central to many important applications spanning from logistics to computational biology. In this paper, we present a general strategy of obtaining highly efficient parallel DP implementations using recursive cache-oblivious divide and conquer technique which turns inflexible kernels into flexible ones (kernels that read from and write to disjoint sub-matrices). We solve four non-trivial DP problems widely used in Bioinformatics, namely the parenthesis problem, Floyd-Warshall's all-pairs shortest paths, gap problem and protein accordion folding using recursive cache-oblivious technique that decompose the original inflexible looping kernel to highly optimizable flexible kernels. To the best of our knowledge no such recursive parallel DP algorithms were known for the protein folding and gap problems. The algorithms are hybrid in the same way as most high-performance matrix multiplication algorithms are recursive with iterative base cases. We show that the base cases of these recursive divide-and-conquer algorithms are predominantly matrix-multiplication-like (MM-like) flexible that expose many optimization opportunities not offered by the traditional looping DP codes. Moreover, the most costly/dominating kernel for these problems are often flexible. As a result, one can obtain highly efficient DP implementations by simply optimizing these kernels. We present a few generic optimization steps that suffices to optimize these DP implementations. Our implementations achieve 5--100x speedup over their standard loop based DP counterparts on modern multicore machines. We also present results on manycores (Xeon Phi) and clusters of multicores obtained by simple extensions for SIMD and shared-distributed-shared-memory architectures, respectively.

High-performance recursive dynamic programming for bioinformatics using MM-like flexible kernels

Stencil computations are widely used to simulate the change of state of physical systems across a multidimensional grid over multiple timesteps. The state-of-the-art techniques in this area fall into three groups: cache-aware tiled looping algorithms, cache-oblivious divide-and-conquer trapezoidal algorithms, and Krylov subspace methods. 
In this paper, we present two efficient parallel algorithms for performing linear stencil computations. Current direct solvers in this domain are computationally inefficient, and Krylov methods require manual labor and mathematical training. We solve these problems for linear stencils by using DFT preconditioning on a Krylov method to achieve a direct solver which is both fast and general. Indeed, while all currently available algorithms for solving general linear stencils perform $\Theta(NT)$ work, where $N$ is the size of the spatial grid and $T$ is the number of timesteps, our algorithms perform $o(NT)$ work. 
To the best of our knowledge, we give the first algorithms that use fast Fourier transforms to compute final grid data by evolving the initial data for many timesteps at once. Our algorithms handle both periodic and aperiodic boundary conditions, and achieve polynomially better performance bounds (i.e., computational complexity and parallel runtime) than all other existing solutions. 
Initial experimental results show that implementations of our algorithms that evolve grids of roughly $10^7$ cells for around $10^5$ timesteps run orders of magnitude faster than state-of-the-art implementations for periodic stencil problems, and 1.3$\times$ to 8.5$\times$ faster for aperiodic stencil problems.

Rezaul Chowdhury

Papers

POSTER: Provably Efficient Scheduling of Cache-Oblivious Wavefront Algorithms

Brief Announcement: Faster Stencil Computations using Gaussian Approximations

A Unified Framework to Discover Permutation Generation Algorithms

High-performance recursive dynamic programming for bioinformatics using MM-like flexible kernels

Fast Stencil Computations using Fast Fourier Transforms