GPU optimizations for a production molecular docking code

Thesis (M.Sc.Eng.) -- Boston UniversityScientists have always felt the desire to perform computationally intensive tasks that surpass the capabilities of conventional single core computers. As a result of this trend, Graphics Processing Units (GPUs) have come to be increasingly used for general computation in scientific research. This field of GPU acceleration is now a vast and mature discipline. Molecular docking, the modeling of the interactions between two molecules, is a particularly computationally intensive task that has been the subject of research for many years. It is a critical simulation tool used for the screening of protein compounds for drug design and in research of the nature of life itself. The PIPER molecular docking program was previously accelerated using GPUs, achieving a notable speedup over conventional single core implementation. Since its original release the development of the CPU based PIPER has not ceased, and it is now a mature and fast parallel code. The GPU version, however, still contains many potential points for optimization. In the current work, we present a new version of GPU PIPER that attains a 3.3x speedup over a parallel MPI version of PIPER running on an 8 core machine and using the optimized Intel Math Kernel Library. We achieve this speedup by optimizing existing kernels for modern GPU architectures and migrating critical code segments to the GPU. In particular, we both improve the runtime of the filtering and scoring stages by more than an order of magnitude, and move all molecular data permanently to the GPU to improve data locality. This new speedup is obtained while retaining a computational accuracy virtually identical to the CPU based version. We also demonstrate that, due to the algorithmic dependencies of the PIPER algorithm on the 3D Fast Fourier Transform, our GPU PIPER will likely remain proportionally faster than equivalent CPU based implementations, and with little room for further optimizations. This new GPU accelerated version of PIPER is integrated as part of the ClusPro molecular docking and analysis server at Boston University. ClusPro has over 4000 registered users and more than 50000 jobs run over the past 4 years

Towards Energy Efficiency in Heterogeneous Processors: Findings on Virtual Screening Methods

The integration of the latest breakthroughs in computational modeling and high performance computing (HPC) has leveraged advances in the fields of healthcare and drug discovery, among others. By integrating all these developments together, scientists are creating new exciting personal therapeutic strategies for living longer that were unimaginable not that long ago. However, we are witnessing the biggest revolution in HPC in the last decade. Several graphics processing unit architectures have established their niche in the HPC arena but at the expense of an excessive power and heat. A solution for this important problem is based on heterogeneity. In this paper, we analyze power consumption on heterogeneous systems, benchmarking a bioinformatics kernel within the framework of virtual screening methods. Cores and frequencies are tuned to further improve the performance or energy efficiency on those architectures. Our experimental results show that targeted low‐cost systems are the lowest power consumption platforms, although the most energy efficient platform and the best suited for performance improvement is the Kepler GK110 graphics processing unit from Nvidia by using compute unified device architecture. Finally, the open computing language version of virtual screening shows a remarkable performance penalty compared with its compute unified device architecture counterpart.Ingeniería, Industria y Construcció

High performance <i>in silico</i> virtual drug screening on many-core processors

Drug screening is an important part of the drug development pipeline for the pharmaceutical industry. Traditional, lab-based methods are increasingly being augmented with computational methods, ranging from simple molecular similarity searches through more complex pharmacophore matching to more computationally intensive approaches, such as molecular docking. The latter simulates the binding of drug molecules to their targets, typically protein molecules. In this work, we describe BUDE, the Bristol University Docking Engine, which has been ported to the OpenCL industry standard parallel programming language in order to exploit the performance of modern many-core processors. Our highly optimized OpenCL implementation of BUDE sustains 1.43 TFLOP/s on a single Nvidia GTX 680 GPU, or 46% of peak performance. BUDE also exploits OpenCL to deliver effective performance portability across a broad spectrum of different computer architectures from different vendors, including GPUs from Nvidia and AMD, Intel’s Xeon Phi and multi-core CPUs with SIMD instruction sets

GPU-optimized approaches to molecular docking-based virtual screening in drug discovery: A comparative analysis

Finding a novel drug is a very long and complex procedure. Using computer simulations, it is possible to accelerate the preliminary phases by performing a virtual screening that filters a large set of drug candidates to a manageable number. This paper presents the implementations and comparative analysis of two GPU-optimized implementations of a virtual screening algorithm targeting novel GPU architectures. This work focuses on the analysis of parallel computation patterns and their mapping onto the target architecture. The first method adopts a traditional approach that spreads the computation for a single molecule across the entire GPU. The second uses a novel batched approach that exploits the parallel architecture of the GPU to evaluate more molecules in parallel. Experimental results showed a different behavior depending on the size of the database to be screened, either reaching a performance plateau sooner or having a more extended initial transient period to achieve a higher throughput (up to 5x), which is more suitable for extreme-scale virtual screening campaigns

Protein-Ligand Complex Generator & Drug Screening via Tiered Tensor Transform

The generation of small molecule candidate (ligand) binding poses in its target protein pocket is important for computer-aided drug discovery. Typical rigid-body docking methods ignore the pocket flexibility of protein, while the more accurate pose generation using molecular dynamics is hindered by slow protein dynamics. We develop a tiered tensor transform (3T) algorithm to rapidly generate diverse protein-ligand complex conformations for both pose and affinity estimation in drug screening, requiring neither machine learning training nor lengthy dynamics computation, while maintaining both coarse-grain-like coordinated protein dynamics and atomistic-level details of the complex pocket. The 3T conformation structures we generate achieve significantly higher accuracy in active ligand classification than traditional ensemble docking using hundreds of experimental protein conformations. Furthermore, we demonstrate that 3T can be used to explore distant protein-ligand binding poses within the protein pocket. 3T structure transformation is decoupled from the system physics, making future usage in other computational scientific domains possible

GPU acceleration of a production molecular docking code

Abstract: Modeling the interactions of biological molecules, or docking, is critical to both understand-ing basic life processes and to designing new drugs. Here we describe the GPU-based acceleration of a recently developed, complex, production docking code. We show how the various functions can be mapped to the GPU and present numerous optimizations. We find which parts of the problem domain are best suited to the different correlation methods. The GPU-accelerated system achieves a speedup of at least 16x for all likely problems sizes. This makes it competitive with FPGA-based systems for small molecule docking, and superior for protein-protein docking.

Exploration of Reaction Pathways and Chemical Transformation Networks

For the investigation of chemical reaction networks, the identification of all relevant intermediates and elementary reactions is mandatory. Many algorithmic approaches exist that perform explorations efficiently and automatedly. These approaches differ in their application range, the level of completeness of the exploration, as well as the amount of heuristics and human intervention required. Here, we describe and compare the different approaches based on these criteria. Future directions leveraging the strengths of chemical heuristics, human interaction, and physical rigor are discussed.Comment: 48 pages, 4 figure

A Performance-Portable SYCL Implementation of CRK-HACC for Exascale

The first generation of exascale systems will include a variety of machine architectures, featuring GPUs from multiple vendors. As a result, many developers are interested in adopting portable programming models to avoid maintaining multiple versions of their code. It is necessary to document experiences with such programming models to assist developers in understanding the advantages and disadvantages of different approaches. To this end, this paper evaluates the performance portability of a SYCL implementation of a large-scale cosmology application (CRK-HACC) running on GPUs from three different vendors: AMD, Intel, and NVIDIA. We detail the process of migrating the original code from CUDA to SYCL and show that specializing kernels for specific targets can greatly improve performance portability without significantly impacting programmer productivity. The SYCL version of CRK-HACC achieves a performance portability of 0.96 with a code divergence of almost 0, demonstrating that SYCL is a viable programming model for performance-portable applications.Comment: 12 pages, 13 figures, 2023 International Workshop on Performance, Portability & Productivity in HP