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Protein-ligand binding is the process by which a small molecule (drug or inhibitor) attaches to a target protein. The binding affinity, which refers to the strength of this interaction, is central to many important problems in bioinformatics such as drug design. An extensive amount of work has been devoted to predicting binding affinity over the past decades due to its significance. In this paper, we review all significant recent works, focusing on the methods, features, and benchmark datasets. We have observed a rising trend in the use of traditional machine learning and deep learning models for predicting binding affinity, accompanied by an increasing amount of data on proteins and small drug-like molecules. While prediction results are constantly improving, we also identify several open questions and potential directions that remain unexplored in the field. This paper could serve as an excellent starting point for machine learning researchers who wish to engage in the study of binding affinity, or for anyone with general interests in machine learning, drug discovery, and bioinformatics.

The urgent need for data democratization in scientific research was the focal point of a panel discussion at SC23 in Denver, Colorado, from November 12 to 17, 2023. This article summarizes the outcomes of that discussion and subsequent conversations. We advocate for strategic investments in financial, human, and technological resources for sustainable data democratization. Emphasizing that data is central to scientific discovery and AI deployment, we highlight barriers such as limited access, inadequate financial incentives for cross-domain collaboration, and a shortage of workforce development initiatives. Our recommendations aim to guide decision-makers in fostering an inclusive research community, breaking down research silos, and developing a skilled workforce to advance scientific discovery., Comment: 5 pages

We report on our experiences replicating 7.3 petabytes (PB) of Earth System Grid Federation (ESGF) climate simulation data from Lawrence Livermore National Laboratory (LLNL) in California to Argonne National Laboratory (ANL) in Illinois and Oak Ridge National Laboratory (ORNL) in Tennessee. This movement of some 29 million files, twice, undertaken in order to establish new ESGF nodes at ANL and ORNL, was performed largely automatically by a simple replication tool, a script that invoked Globus to transfer large bundles of files while tracking progress in a database. Under the covers, Globus organized transfers to make efficient use of the high-speed Energy Sciences network (ESnet) and the data transfer nodes deployed at participating sites, and also addressed security, integrity checking, and recovery from a variety of transient failures. This success demonstrates the considerable benefits that can accrue from the adoption of performant data replication infrastructure.

Experimental science is increasingly driven by instruments that produce vast volumes of data and thus a need to manage, compute, describe, and index this data. High performance and distributed computing provide the means of addressing the computing needs; however, in practice, the variety of actions required and the distributed set of resources involved, requires sophisticated "flows" defining the steps to be performed on data. As each scan or measurement is performed by an instrument, a new instance of the flow is initiated resulting in a "fleet" of concurrently running flows, with the overall goal to process all the data collected during a potentially long-running experiment. During the course of the experiment, each flow may need to adapt its execution due to changes in the environment, such as computational or storage resource availability, or based on the progress of the fleet as a whole such as completion or discovery of an intermediate result leading to a change in subsequent flow's behavior. We introduce a cloud-based decision engine, Braid, which flows consult during execution to query their run-time environment and coordinate with other flows within their fleet. Braid accepts streams of measurements taken from the run-time environment or from within flow runs which can then be statistically aggregated and compared to other streams to determine a strategy to guide flow execution. For example, queue lengths in execution environments can be used to direct a flow to run computations in one environment or another, or experiment progress as measured by individual flows can be aggregated to determine the progress and subsequent direction of the flows within a fleet. We describe Braid, its interface, implementation and performance characteristics. We further show through examples and experience modifying an existing scientific flow how Braid is used to make adaptable flows.

High-energy X-ray diffraction methods can non-destructively map the 3D microstructure and associated attributes of metallic polycrystalline engineering materials in their bulk form. These methods are often combined with external stimuli such as thermo-mechanical loading to take snapshots over time of the evolving microstructure and attributes. However, the extreme data volumes and the high costs of traditional data acquisition and reduction approaches pose a barrier to quickly extracting actionable insights and improving the temporal resolution of these snapshots. Here we present a fully automated technique capable of rapidly detecting the onset of plasticity in high-energy X-ray microscopy data. Our technique is computationally faster by at least 50 times than the traditional approaches and works for data sets that are up to 9 times sparser than a full data set. This new technique leverages self-supervised image representation learning and clustering to transform massive data into compact, semantic-rich representations of visually salient characteristics (e.g., peak shapes). These characteristics can be a rapid indicator of anomalous events such as changes in diffraction peak shapes. We anticipate that this technique will provide just-in-time actionable information to drive smarter experiments that effectively deploy multi-modal X-ray diffraction methods that span many decades of length scales.

Self-driving labs (SDLs) leverage combinations of artificial intelligence, automation, and advanced computing to accelerate scientific discovery. The promise of this field has given rise to a rich community of passionate scientists, engineers, and social scientists, as evidenced by the development of the Acceleration Consortium and recent Accelerate Conference. Despite its strengths, this rapidly developing field presents numerous opportunities for growth, challenges to overcome, and potential risks of which to remain aware. This community perspective builds on a discourse instantiated during the first Accelerate Conference, and looks to the future of self-driving labs with a tempered optimism. Incorporating input from academia, government, and industry, we briefly describe the current status of self-driving labs, then turn our attention to barriers, opportunities, and a vision for what is possible. Our field is delivering solutions in technology and infrastructure, artificial intelligence and knowledge generation, and education and workforce development. In the spirit of community, we intend for this work to foster discussion and drive best practices as our field grows.

Coherent microscopy techniques provide an unparalleled multi-scale view of materials across scientific and technological fields, from structural materials to quantum devices, from integrated circuits to biological cells. Driven by the construction of brighter sources and high-rate detectors, coherent X-ray microscopy methods like ptychography are poised to revolutionize nanoscale materials characterization. However, associated significant increases in data and compute needs mean that conventional approaches no longer suffice for recovering sample images in real-time from high-speed coherent imaging experiments. Here, we demonstrate a workflow that leverages artificial intelligence at the edge and high-performance computing to enable real-time inversion on X-ray ptychography data streamed directly from a detector at up to 2 kHz. The proposed AI-enabled workflow eliminates the sampling constraints imposed by traditional ptychography, allowing low dose imaging using orders of magnitude less data than required by traditional methods.

In order to take full advantage of the U.S. Department of Energy's billion-dollar investments into the next-generation research infrastructure (e.g., exascale, light sources, colliders), advances are required not only in detector technology but also in computing and specifically AI. Let us consider an example from X-ray science. Nanoscale X-ray imaging is a crucial tool to enable a wide range of scientific explorations from materials science and biology to mechanical and civil engineering. The next-generation light sources will increase the X-ray beam brightness and coherent flux by 100 to 1,000 times. In order to image larger samples, the continuous frame rate of pixel array detectors must be increased, approaching 1 MHz, which requires several Tbps (aggregated) to transfer pixel data out to a data acquisition system. Using 65-nm CMOS technology, an optimistic raw data rate off such a chip is about 100-200 Gbps. However, a continuous 1 MHz detector with only $256 \times 256$ pixels at 16-bit resolution, for example, will require 1,000 Gbps (i.e., 1 Tbps) bandwidth off the chip! It is impractical to have multiple high-speed transceivers running in parallel to provide such bandwidth and represents the first data bottleneck. New approaches are necessary to reduce the data size by performing data compression or AI-based feature extraction directly inside a detector silicon chip in a streaming manner before sending it off-chip., Comment: White paper for AI@DOE Roundtable, December 8-9, 2021 (virtual). arXiv admin note: text overlap with arXiv:2110.07828

Beamlines at synchrotron light source facilities are powerful scientific instruments used to image samples and observe phenomena at high spatial and temporal resolutions. Typically, these facilities are equipped only with modest compute resources for the analysis of generated experimental datasets. However, high data rate experiments can easily generate data in volumes that take days (or even weeks) to process on those local resources. To address this challenge, we present a system that unifies leadership computing and experimental facilities by enabling the automated establishment of data analysis pipelines that extend from edge data acquisition systems at synchrotron beamlines to remote computing facilities; under the covers, our system uses Globus Auth authentication to minimize user interaction, funcX to run user-defined functions on supercomputers, and Globus Flows to define and execute workflows. We describe the application of this system to ptychography, an ultra-high-resolution coherent diffraction imaging technique that can produce 100s of gigabytes to terabytes in a single experiment. When deployed on the DGX A100 ThetaGPU cluster at the Argonne Leadership Computing Facility and a microscopy beamline at the Advanced Photon Source, our system performs analysis as an experiment progresses to provide timely feedback., Comment: 19 pages, 5 figures, to be published in Smoky Mountains Computational Sciences and Engineering Conference (SMC 2021)

Scripting languages such as Python and R have been widely adopted as tools for the productive development of scientific software because of the power and expressiveness of the languages and available libraries. However, deploying scripted applications on large-scale parallel computer systems such as the IBM Blue Gene/Q or Cray XE6 is a challenge because of issues including operating system limitations, interoperability challenges, parallel filesystem overheads due to the small file system accesses common in scripted approaches, and other issues. We present here a new approach to these problems in which the Swift scripting system is used to integrate high-level scripts written in Python, R, and Tcl, with native code developed in C, C++, and Fortran, by linking Swift to the library interfaces to the script interpreters. In this approach, Swift handles data management, movement, and marshaling among distributed-memory processes without direct user manipulation of low-level communication libraries such as MPI. We present a technique to efficiently launch scripted applications on large-scale supercomputers using a hierarchical programming model., Comment: 2015 IEEE International Conference on Cluster Computing

While past information technology (IT) advances have transformed society, future advances hold even greater promise. For example, we have only just begun to reap the changes from artificial intelligence (AI), especially machine learning (ML). Underlying IT's impact are the dramatic improvements in computer hardware, which deliver performance that unlock new capabilities. For example, recent successes in AI/ML required the synergy of improved algorithms and hardware architectures (e.g., general-purpose graphics processing units). However, unlike in the 20th Century and early 2000s, tomorrow's performance aspirations must be achieved without continued semiconductor scaling formerly provided by Moore's Law and Dennard Scaling. How will one deliver the next 100x improvement in capability at similar or less cost to enable great value? Can we make the next AI leap without 100x better hardware? This whitepaper argues for a multipronged effort to develop new computing approaches beyond Moore's Law to advance the foundation that computing provides to US industry, education, medicine, science, and government. This impact extends far beyond the IT industry itself, as IT is now central for providing value across society, for example in semi-autonomous vehicles, tele-education, health wearables, viral analysis, and efficient administration. Herein we draw upon considerable visioning work by CRA's Computing Community Consortium (CCC) and the IEEE Rebooting Computing Initiative (IEEE RCI), enabled by thought leader input from industry, academia, and the US government., Comment: A Computing Community Consortium (CCC) white paper, 4 pages

Synchrotron-based X-ray computed tomography is widely used for investigating inner structures of specimens at high spatial resolutions. However, potential beam damage to samples often limits the X-ray exposure during tomography experiments. Proposed strategies for eliminating beam damage also decrease reconstruction quality. Here we present a deep learning-based method to enhance low-dose tomography reconstruction via a hybrid-dose acquisition strategy composed of extremely sparse-view normal-dose projections and full-view low-dose projections. Corresponding image pairs are extracted from low-/normal-dose projections to train a deep convolutional neural network, which is then applied to enhance full-view noisy low-dose projections. Evaluation on two experimental datasets under different hybrid-dose acquisition conditions show significantly improved structural details and reduced noise levels compared to uniformly distributed acquisitions with the same number of total dosage. The resulting reconstructions also preserve more structural information than reconstructions processed with traditional analytical and regularization-based iterative reconstruction methods from uniform acquisitions. Our performance comparisons show that our implementation, HDrec, can perform denoising of a real-world experimental data 410x faster than the state-of-the-art Xlearn method while providing better quality. This framework can be applied to other tomographic or scanning based X-ray imaging techniques for enhanced analysis of dose-sensitive samples and has great potential for studying fast dynamic processes., Comment: 9 pages, 8 figures, accepted by Workshop on Artificial Intelligence an Machine Learning for Scientific Applications 2020 (AI4S20)

X-ray computed tomography is a commonly used technique for noninvasive imaging at synchrotron facilities. Iterative tomographic reconstruction algorithms are often preferred for recovering high quality 3D volumetric images from 2D X-ray images, however, their use has been limited to small/medium datasets due to their computational requirements. In this paper, we propose a high-performance iterative reconstruction system for terabyte(s)-scale 3D volumes. Our design involves three novel optimizations: (1) optimization of (back)projection operators by extending the 2D memory-centric approach to 3D; (2) performing hierarchical communications by exploiting "fat-node" architecture with many GPUs; (3) utilization of mixed-precision types while preserving convergence rate and quality. We extensively evaluate the proposed optimizations and scaling on the Summit supercomputer. Our largest reconstruction is a mouse brain volume with 9Kx11Kx11K voxels, where the total reconstruction time is under three minutes using 24,576 GPUs, reaching 65 PFLOPS: 34% of Summit's peak performance.

Training neural networks with many processors can reduce time-to-solution; however, it is challenging to maintain convergence and efficiency at large scales. The Kronecker-factored Approximate Curvature (K-FAC) was recently proposed as an approximation of the Fisher Information Matrix that can be used in natural gradient optimizers. We investigate here a scalable K-FAC design and its applicability in convolutional neural network (CNN) training at scale. We study optimization techniques such as layer-wise distribution strategies, inverse-free second-order gradient evaluation, and dynamic K-FAC update decoupling to reduce training time while preserving convergence. We use residual neural networks (ResNet) applied to the CIFAR-10 and ImageNet-1k datasets to evaluate the correctness and scalability of our K-FAC gradient preconditioner. With ResNet-50 on the ImageNet-1k dataset, our distributed K-FAC implementation converges to the 75.9% MLPerf baseline in 18-25% less time than does the classic stochastic gradient descent (SGD) optimizer across scales on a GPU cluster., Comment: To be published in the proceedings of the International Conference for High Performance Computing, Networking, Storage and Analysis (SC20)