Application Experiences on a GPU-Accelerated Arm-based HPC Testbed.

This paper assesses and reports the experience of ten teams working to port, validate, and benchmark several High Performance Computing applications on a novel GPU-accelerated Arm testbed system. The testbed consists of eight NVIDIA Arm HPC Developer Kit systems, each one equipped with a server-class Arm CPU from Ampere Computing and two data center GPUs from NVIDIA Corp. The systems are connected together using InfiniBand interconnect.

Dynamics of chromosome organization in a minimal bacterial cell.

Computational models of cells cannot be considered complete unless they include the most fundamental process of life, the replication and inheritance of genetic material. By creating a computational framework to model systems of replicating bacterial chromosomes as polymers at 10 bp resolution with Brownian dynamics, we investigate changes in chromosome organization during replication and extend the applicability of an existing whole-cell model (WCM) for a genetically minimal bacterium, JCVI-syn3A, to the entire cell-cycle. To achieve cell-scale chromosome structures that are realistic, we model the chromosome as a self-avoiding homopolymer with bending and torsional stiffnesses that capture the essential mechanical properties of dsDNA in Syn3A.

VMD as a Platform for Interactive Small Molecule Preparation and Visualization in Quantum and Classical Simulations.

Modeling and simulation of small molecules such as drugs and biological cofactors have been both a major focus of computational chemistry for decades and a growing need among computational biophysicists who seek to investigate the interaction of different types of ligands with biomolecules. Of particular interest in this regard are quantum mechanical (QM) calculations that are used to more accurately describe such small molecules, which can be of heterogeneous structures and chemistry, either in purely QM calculations or in hybrid QM/molecular mechanics (MM) simulations. QM programs are also used to develop MM force field parameters for small molecules to be used along with established force fields for biomolecules in classical simulations.

Lessons Learned from Responsive Molecular Dynamics Studies of the COVID-19 Virus.

Over the past 18 months, the need to perform atomic detail molecular dynamics simulations of the SARS-CoV-2 virion, its spike protein, and other structures related to the viral infection cycle has led biomedical researchers worldwide to urgently seek out all available biomolecular structure information, appropriate molecular modeling and simulation software, and the necessary computing resources to conduct their work. We describe our experiences from several COVID-19 research collaborations and the challenges they presented in terms of our molecular modeling software development and support efforts, our laboratory's local computing environment, and our scientists' use of non-traditional HPC hardware platforms such as public clouds for large scale parallel molecular dynamics simulations.

ANARI: A 3-D Rendering API Standard.

ANARI is a new 3-D rendering API, an emerging Khronos standard that enables visualization applications to leverage the state-of-the-art rendering techniques across diverse hardware platforms and rendering engines. Visualization applications have historically embedded custom-written renderers to enable them to provide the necessary combination of features, performance, and visual fidelity required by their users. As computing power, rendering algorithms, dedicated rendering hardware acceleration operations, and associated low-level APIs have advanced, the effort and costs associated with maintaining renderers within visualization applications have risen dramatically.

Intelligent resolution: Integrating Cryo-EM with AI-driven multi-resolution simulations to observe the severe acute respiratory syndrome coronavirus-2 replication-transcription machinery in action.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replication transcription complex (RTC) is a multi-domain protein responsible for replicating and transcribing the viral mRNA inside a human cell. Attacking RTC function with pharmaceutical compounds is a pathway to treating COVID-19. Conventional tools, e.

py-MCMD: Python Software for Performing Hybrid Monte Carlo/Molecular Dynamics Simulations with GOMC and NAMD.

py-MCMD, an open-source Python software, provides a robust workflow layer that manages communication of relevant system information between the simulation engines NAMD and GOMC and generates coherent thermodynamic properties and trajectories for analysis. To validate the workflow and highlight its capabilities, hybrid Monte Carlo/molecular dynamics (MC/MD) simulations are performed for SPC/E water in the isobaric-isothermal () and grand canonical (GC) ensembles as well as with Gibbs ensemble Monte Carlo (GEMC). The hybrid MC/MD approach shows close agreement with reference MC simulations and has a computational efficiency that is 2 to 136 times greater than traditional Monte Carlo simulations.

AI-driven multiscale simulations illuminate mechanisms of SARS-CoV-2 spike dynamics.

We develop a generalizable AI-driven workflow that leverages heterogeneous HPC resources to explore the time-dependent dynamics of molecular systems. We use this workflow to investigate the mechanisms of infectivity of the SARS-CoV-2 spike protein, the main viral infection machinery. Our workflow enables more efficient investigation of spike dynamics in a variety of complex environments, including within a complete SARS-CoV-2 viral envelope simulation, which contains 305 million atoms and shows strong scaling on ORNL Summit using NAMD.

Scalable Analysis of Authentic Viral Envelopes on FRONTERA.

Enveloped viruses, such as SARS-CoV-2, infect cells via fusion of their envelope with the host membrane. By employing molecular simulations to characterize viral envelopes, researchers can gain insights into key determinants of infection. Here, the Frontera supercomputer is leveraged for large-scale modeling and analysis of authentic viral envelopes, whose lipid compositions are complex and realistic.

AI-Driven Multiscale Simulations Illuminate Mechanisms of SARS-CoV-2 Spike Dynamics.

We develop a generalizable AI-driven workflow that leverages heterogeneous HPC resources to explore the time-dependent dynamics of molecular systems. We use this workflow to investigate the mechanisms of infectivity of the SARS-CoV-2 spike protein, the main viral infection machinery. Our workflow enables more efficient investigation of spike dynamics in a variety of complex environments, including within a complete SARS-CoV-2 viral envelope simulation, which contains 305 million atoms and shows strong scaling on ORNL Summit using NAMD.

Scalable molecular dynamics on CPU and GPU architectures with NAMD.

NAMDis a molecular dynamics program designed for high-performance simulations of very large biological objects on CPU- and GPU-based architectures. NAMD offers scalable performance on petascale parallel supercomputers consisting of hundreds of thousands of cores, as well as on inexpensive commodity clusters commonly found in academic environments. It is written in C++ and leans on Charm++ parallel objects for optimal performance on low-latency architectures.

Multiscale modeling and cinematic visualization of photosynthetic energy conversion processes from electronic to cell scales.

Conversion of sunlight into chemical energy, namely photosynthesis, is the primary energy source of life on Earth. A visualization depicting this process, based on multiscale computational models from electronic to cell scales, is presented in the form of an excerpt from the fulldome show . This accessible visual narrative shows a lay audience, including children, how the energy of sunlight is captured, converted, and stored through a chain of proteins to power living cells.

High-Performance Analysis of Biomolecular Containers to Measure Small-Molecule Transport, Transbilayer Lipid Diffusion, and Protein Cavities.

Compartmentalization is a central theme in biology. Cells are composed of numerous membrane-enclosed structures, evolved to facilitate specific biochemical processes; viruses act as containers of genetic material, optimized to drive infection. Molecular dynamics simulations provide a mechanism to study biomolecular containers and the influence they exert on their environments; however, trajectory analysis software generally lacks knowledge of container interior versus exterior.

NAMD goes quantum: an integrative suite for hybrid simulations.

Hybrid methods that combine quantum mechanics (QM) and molecular mechanics (MM) can be applied to studies of reaction mechanisms in locations ranging from active sites of small enzymes to multiple sites in large bioenergetic complexes. By combining the widely used molecular dynamics and visualization programs NAMD and VMD with the quantum chemistry packages ORCA and MOPAC, we created an integrated, comprehensive, customizable, and easy-to-use suite (http://www.ks.

Challenges of Integrating Stochastic Dynamics and Cryo-Electron Tomograms in Whole-Cell Simulations.

Cryo-electron tomography (cryo-ET) has rapidly emerged as a powerful tool to investigate the internal, three-dimensional spatial organization of the cell. In parallel, the GPU-based technology to perform spatially resolved stochastic simulations of whole cells has arisen, allowing the simulation of complex biochemical networks over cell cycle time scales using data taken from -omics, single molecule experiments, and in vitro kinetics. By using real cell geometry derived from cryo-ET data, we have the opportunity to imbue these highly detailed structural data-frozen in time-with realistic biochemical dynamics and investigate how cell structure affects the behavior of the embedded chemical reaction network.

Immersive Molecular Visualization with Omnidirectional Stereoscopic Ray Tracing and Remote Rendering.

Immersive molecular visualization provides the viewer with intuitive perception of complex structures and spatial relationships that are of critical interest to structural biologists. The recent availability of commodity head mounted displays (HMDs) provides a compelling opportunity for widespread adoption of immersive visualization by molecular scientists, but HMDs pose additional challenges due to the need for low-latency, high-frame-rate rendering. State-of-the-art molecular dynamics simulations produce terabytes of data that can be impractical to transfer from remote supercomputers, necessitating routine use of remote visualization.

High Performance Molecular Visualization: In-Situ and Parallel Rendering with EGL.

Large scale molecular dynamics simulations produce terabytes of data that is impractical to transfer to remote facilities. It is therefore necessary to perform visualization tasks in-situ as the data are generated, or by running interactive remote visualization sessions and batch analyses co-located with direct access to high performance storage systems. A significant challenge for deploying visualization software within clouds, clusters, and supercomputers involves the operating system software required to initialize and manage graphics acceleration hardware.

Evaluation of Emerging Energy-Efficient Heterogeneous Computing Platforms for Biomolecular and Cellular Simulation Workloads.

Many of the continuing scientific advances achieved through computational biology are predicated on the availability of ongoing increases in computational power required for detailed simulation and analysis of cellular processes on biologically-relevant timescales. A critical challenge facing the development of future exascale supercomputer systems is the development of new computing hardware and associated scientific applications that dramatically improve upon the energy efficiency of existing solutions, while providing increased simulation, analysis, and visualization performance. Mobile computing platforms have recently become powerful enough to support interactive molecular visualization tasks that were previously only possible on laptops and workstations, creating future opportunities for their convenient use for meetings, remote collaboration, and as head mounted displays for immersive stereoscopic viewing.

Molecular dynamics-based refinement and validation for sub-5 Å cryo-electron microscopy maps.

Two structure determination methods, based on the molecular dynamics flexible fitting (MDFF) paradigm, are presented that resolve sub-5 Å cryo-electron microscopy (EM) maps with either single structures or ensembles of such structures. The methods, denoted cascade MDFF and resolution exchange MDFF, sequentially re-refine a search model against a series of maps of progressively higher resolutions, which ends with the original experimental resolution. Application of sequential re-refinement enables MDFF to achieve a radius of convergence of ~25 Å demonstrated with the accurate modeling of β-galactosidase and TRPV1 proteins at 3.

Atomic Detail Visualization of Photosynthetic Membranes with GPU-Accelerated Ray Tracing.

The cellular process responsible for providing energy for most life on Earth, namely photosynthetic light-harvesting, requires the cooperation of hundreds of proteins across an organelle, involving length and time scales spanning several orders of magnitude over quantum and classical regimes. Simulation and visualization of this fundamental energy conversion process pose many unique methodological and computational challenges. We present, in two accompanying movies, light-harvesting in the photosynthetic apparatus found in purple bacteria, the so-called chromatophore.

Early Experiences Porting the NAMD and VMD Molecular Simulation and Analysis Software to GPU-Accelerated OpenPOWER Platforms.

All-atom molecular dynamics simulations of biomolecules provide a powerful tool for exploring the structure and dynamics of large protein complexes within realistic cellular environments. Unfortunately, such simulations are extremely demanding in terms of their computational requirements, and they present many challenges in terms of preparation, simulation methodology, and analysis and visualization of results. We describe our early experiences porting the popular molecular dynamics simulation program NAMD and the simulation preparation, analysis, and visualization tool VMD to GPU-accelerated OpenPOWER hardware platforms.

QwikMD - Integrative Molecular Dynamics Toolkit for Novices and Experts.

The proper functioning of biomolecules in living cells requires them to assume particular structures and to undergo conformational changes. Both biomolecular structure and motion can be studied using a wide variety of techniques, but none offers the level of detail as do molecular dynamics (MD) simulations. Integrating two widely used modeling programs, namely NAMD and VMD, we have created a robust, user-friendly software, QwikMD, which enables novices and experts alike to address biomedically relevant questions, where often only molecular dynamics simulations can provide answers.

TopoGromacs: Automated Topology Conversion from CHARMM to GROMACS within VMD.

Molecular dynamics (MD) simulation engines use a variety of different approaches for modeling molecular systems with force fields that govern their dynamics and describe their topology. These different approaches introduce incompatibilities between engines, and previously published software bridges the gaps between many popular MD packages, such as between CHARMM and AMBER or GROMACS and LAMMPS. While there are many structure building tools available that generate topologies and structures in CHARMM format, only recently have mechanisms been developed to convert their results into GROMACS input.

Runtime and Architecture Support for Efficient Data Exchange in Multi-Accelerator Applications.

Heterogeneous parallel computing applications often process large data sets that require multiple GPUs to jointly meet their needs for physical memory capacity and compute throughput. However, the lack of high-level abstractions in previous heterogeneous parallel programming models force programmers to resort to multiple code versions, complex data copy steps and synchronization schemes when exchanging data between multiple GPU devices, which results in high software development cost, poor maintainability, and even poor performance. This paper describes the HPE runtime system, and the associated architecture support, which enables a simple, efficient programming interface for exchanging data between multiple GPUs through either interconnects or cross-node network interfaces.