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

Bioinformatics

This book is divided into different research areas relevant in Bioinformatics such as biological networks, next generation sequencing, high performance computing, molecular modeling, structural bioinformatics, molecular modeling and intelligent data analysis. Each book section introduces the basic concepts and then explains its application to problems of great relevance, so both novice and expert readers can benefit from the information and research works presented here

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

2020 NASA Technology Taxonomy

This document is an update (new photos used) of the PDF version of the 2020 NASA Technology Taxonomy that will be available to download on the OCT Public Website. The updated 2020 NASA Technology Taxonomy, or "technology dictionary", uses a technology discipline based approach that realigns like-technologies independent of their application within the NASA mission portfolio. This tool is meant to serve as a common technology discipline-based communication tool across the agency and with its partners in other government agencies, academia, industry, and across the world

Swarm Robotics

Collectively working robot teams can solve a problem more efficiently than a single robot, while also providing robustness and flexibility to the group. Swarm robotics model is a key component of a cooperative algorithm that controls the behaviors and interactions of all individuals. The robots in the swarm should have some basic functions, such as sensing, communicating, and monitoring, and satisfy the following properties

Text-basierte Ähnlichkeitssuche zur Treffer- und Leitstruktur-Identifizierung

This work investigated the applicability of global pairwise sequence alignment to the detection of functional analogues in virtual screening. This variant of sequence comparison was developed for the identification of homologue proteins based on amino acid or nucleotide sequences. Because of the significant differences between biopolymers and small molecules several aspects of this approach for sequence comparison had to be adapted. All proposed concepts were implemented as the ‘Pharmacophore Alignment Search Tool’ (PhAST) and evaluated in retrospective experiments on the COBRA dataset in version 6.1. The aim to identify functional analogues raised the necessity for identification and classification of functional properties in molecular structures. This was realized by fragment-based atom-typing, where one out of nine functional properties was assigned to each non-hydrogen atom in a structure. These properties were pre-assigned to atoms in the fragments. Whenever a fragment matched a substructure in a molecule, the assigned properties were transferred from fragment atoms to structure atoms. Each functional property was represented by exactly one symbol. Unlike amino acid or nucleotide sequences, small drug-like molecules contain branches and cycles. This was a major obstacle in the application of sequence alignment to virtual screening, since this technique can only be applied to linear sequences of symbols. The best linearization technique was shown to be Minimum Volume Embedding. To the best of knowledge, this work represents the first application of dimensionality reduction to graph linearization. Sequence alignment relies on a scoring system that rates symbol equivalences (matches) and differences (mismatches) based on functional properties that correspond to rated symbols. Existing scoring schemes are applicable only to amino acids and nucleotides. In this work, scoring schemes for functional properties in drug-like molecules were developed based on property frequencies and isofunctionality judged from chemical experience, pairwise sequence alignments, pairwise kernel-based assignments and stochastic optimization. The scoring system based on property frequencies and isofunctionality proved to be the most powerful (measured in enrichment capability). All developed scoring systems performed superior compared to simple scoring approaches that rate matches and mismatches uniformly. The frameworks proposed for score calculations can be used to guide modifications to the atom-typing in promising directions. The scoring system was further modified to allow for emphasis on particular symbols in a sequence. It was proven that the application of weights to symbols that correspond to key interaction points important to receptor-ligand-interaction significantly improves screening capabilities of PhAST. It was demonstrated that the systematic application of weights to all sequence positions in retrospective experiments can be used for pharmacophore elucidation. A scoring system based on structural instead of functional similarity was investigated and found to be suitable for similarity searches in shape-constrained datasets. Three methods for similarity assessment based on alignments were evaluated: Sequence identity, alignment score and significance. PhAST achieved significantly higher enrichment with alignment scores compared to sequence identity. p-values as significance estimates were calculated in a combination of Marcov Chain Monte Carlo Simulation and Importance Sampling. p-values were adapted to library size in a Bonferroni correction, yielding E-values. A significance threshold of an E-value of 1*10-5 was proposed for the application in prospective screenings. PhAST was compared to state-of-the-art methods for virtual screening. The unweighted version was shown to exhibit comparable enrichment capabilities. Compound rankings obtained with PhAST were proven to be complementary to those of other methods. The application to three-dimensional instead of two-dimensional molecular representations resulted in altered compound rankings without increased enrichment. PhAST was employed in two prospective applications. A screening for non-nucleoside analogue inhibitors of bacterial thymidin kinase yielded a hit with a distinct structural framework but only weak activity. The search for drugs not member of the NSAID (non-steroidal anti-inflammatory drug) class as modulators of gamma-secretase resulted in a potent modulator with clear structural distiction from the reference compound. The calculation of significance estimates, emphasizing on key interactions, the pharmacophore elucidation capabilities and the unique compound rannkings set PhAST apart from other screening techniques.In dieser Arbeit wurde die Anwendbarkeit von paarweisem globalen Sequenzalignment auf das Problem des Molekülsvergleichs im virtuellen Screening untersucht, einem Teilgebiet der computerbasierten Wirkstoffentwicklung. Sequenzalignment wurde zur Identifizierung homologer Proteine entwickelt. Bisher wurde es nur angewendet auf Sequenzen aus Aminosäuren oder Nukleotiden. Aufgrund der Unterschiede zwischen Biopolymeren und wirkstoffartigen Molekülen wurde dieser Ansatz zum Sequenzvergleich modifiziert und auf die konkrete Problemstellung angepasst. Alle vorgestellten und untersuchten Methoden wurden implementiert unter dem Namen ‚Pharmacophore Alignment Search Tool’ (PhAST). Zielsetzung bei der Entwicklung von PhAST war es, die funktionelle Ähnlichkeit zwischen Molekülen zu berechnen. Dafür war es notwendig, einen Ansatz zu implementieren, der den Atomen eines Moleküls funktionelle Eigenschaften zuweist. Dies wurde realisiert durch eine auf Fragmenten basierende Atomtypisierung. Den Atomen einer Sammlung vordefinierter Fragmente wurden nach bestem Wissen und Gewissen Eigenschaften zugewiesen. In jedem Fall, in dem eines der Fragmente als Substruktur eines Moleküls auftrat, wurden die Atomtypisierungen von dem jeweiligen Fragment auf die Atome des Moleküls übertragen. Insgesamt unterscheidet PhAST neun funktionelle Eigenschaften und deren Kombination, wobei jedem Atomtyp genau ein Symbol zugeordnet ist. Im Gegensatz zu Sequenzen von Aminosäuren und Nukleotiden sind wirkstoffartige Moleküle verzweigt, ungerichtet und enthalten Ringeschlüsse. Sequenzalignment ist aber ausschließlich auf lineare Sequenzen anwendbar. Folglich mussten Moleküle mit ihren funktionellen Eigenschaften zunächst in einer linearisierten Form gespeichert werden. Es wurde gezeigt, dass Minimum Volume Embedding die performanteste der getesteten Linearisierungsmethoden war. Nach bestem Wissen und Gewissen wurden in dieser Arbeit zum ersten mal Methoden zur Dimensionsreduktion auf das Problem der kanonischen Indizierung von Graphen angewendet. Zur Berechnung von Sequenzalignments ist ein Bewertungssystem von Equivalenzen und Unterschieden von Symbolen notwendig. Die bestehenden Systeme sind nur anwendbar auf Aminosäuren und Nukleotide. Daher wurde ein Bewertungssystem für Atomeigenschaften nach chemischer Intuition entwickelt, sowie drei automatisierte Methoden, solche Systeme zu berechnen. Das nach chemischer Intuition erstellte Bewertungsschema wurde als den anderen signifikant überlegen identifiziert. Die Flexibilität des Bewertungssystems in globalem Sequenzalignment machte es möglich, Symbole die berechneten Alignments stärker beeinflussen zu lassen, von denen bekannt war, dass sie für essentielle Wechselwirkungen in der Rezeptor-Ligand-Interaktion stehen. Es wurde gezeigt, dass diese Gewichtung die Screening Fähigkeiten von PhAST signifikant steigerte. Weiterhin konnte gezeigt werden, dass PhAST mit der systematischen Anwendung von Gewichten auf alle Sequenzpositionen in der Lage war, essentielle Wechselwirkungen für die Rezeptor-Ligand-Interaktion zu identifizieren. Bedingung hierfür war jedoch, dass ein geeigneter Datensatz mit aktiven und inaktiven Substanzen zur Verfügung stand. In dieser Arbeit wurden verschiedene Methoden evaluiert, mit denen aus Alignments Ähnlichkeiten berechnet werden können: Sequenzidentität, Alignment Score und p-Werte. Es wurde gezeigt, dass der Alignmentscore der Sequenzidentität für die Verwendung in PhAST signifikant überlegen ist. Für die Berechnung von p-Werten zur Bestimmung der Signfifikanz von Alignments musste zunächst die Verteilung von Alignment Scores für zufällige Sequenzen bestimmter Längen bestimmt werden. Dies geschah mit einer Kombination aus ‚Marcov Chain Monte Carlo Simulation’ und ‚Importance Sampling’. Die berechneten p-Werte wurden einer Bonferroni Korrektur unterzogen, und so unter Berücksichtigung der Gesamtzahl von im virtuellen Screening verglichenen Molekülen zu E-Werten. Als Ergebnis dieser Arbeit wird ein E-Wert von 1*10-5 als Grenzwert vorgeschlagen, wobei Alignments mit geringeren E-Werten als signifikant anzuerkennen sind. PhAST wurde in retrospektiven Screening mit anderen Methoden zum virtuellen Screening verglichen. Es konnte gezeigt werden, dass seine Fähigkeiten zur Identifizierung funktioneller Analoga mit denen der besten anderen Methoden vergleichbar oder ihnen sogar überlegen ist. Es konnte gezeigt werden, dass nach von PhAST berechneten Ähnlichkeiten sortierte Molekülsammlungen von den Sortierungen anderer Methoden abweichen. Im Rahmen dieser Arbeit wurde PhAST erfolgreich in zwei prospektiven Anwendungen eingesetzt. So wurde ein schwacher Inhibitor der bakteriellen Thymidinkinase identifiziert, der kein Nukleosid Analogon ist. In einem Screening nach Modulatoren der Gamma-Sekretase wurde ein potentes Molekül identifiziert, das deutliche strukturelle Unterschiede zur verwendeten Referenz aufwies

Aerial Vehicles

This book contains 35 chapters written by experts in developing techniques for making aerial vehicles more intelligent, more reliable, more flexible in use, and safer in operation.It will also serve as an inspiration for further improvement of the design and application of aeral vehicles. The advanced techniques and research described here may also be applicable to other high-tech areas such as robotics, avionics, vetronics, and space

High-Performance Modelling and Simulation for Big Data Applications

This open access book was prepared as a Final Publication of the COST Action IC1406 “High-Performance Modelling and Simulation for Big Data Applications (cHiPSet)“ project. Long considered important pillars of the scientific method, Modelling and Simulation have evolved from traditional discrete numerical methods to complex data-intensive continuous analytical optimisations. Resolution, scale, and accuracy have become essential to predict and analyse natural and complex systems in science and engineering. When their level of abstraction raises to have a better discernment of the domain at hand, their representation gets increasingly demanding for computational and data resources. On the other hand, High Performance Computing typically entails the effective use of parallel and distributed processing units coupled with efficient storage, communication and visualisation systems to underpin complex data-intensive applications in distinct scientific and technical domains. It is then arguably required to have a seamless interaction of High Performance Computing with Modelling and Simulation in order to store, compute, analyse, and visualise large data sets in science and engineering. Funded by the European Commission, cHiPSet has provided a dynamic trans-European forum for their members and distinguished guests to openly discuss novel perspectives and topics of interests for these two communities. This cHiPSet compendium presents a set of selected case studies related to healthcare, biological data, computational advertising, multimedia, finance, bioinformatics, and telecommunications

Improving Performance and Energy Efficiency of Heterogeneous Systems with rCUDA

Tesis por compendio[ES] En la última década la utilización de la GPGPU (General Purpose computing in Graphics Processing Units; Computación de Propósito General en Unidades de Procesamiento Gráfico) se ha vuelto tremendamente popular en los centros de datos de todo el mundo. Las GPUs (Graphics Processing Units; Unidades de Procesamiento Gráfico) se han establecido como elementos aceleradores de cómputo que son usados junto a las CPUs formando sistemas heterogéneos. La naturaleza masivamente paralela de las GPUs, destinadas tradicionalmente al cómputo de gráficos, permite realizar operaciones numéricas con matrices de datos a gran velocidad debido al gran número de núcleos que integran y al gran ancho de banda de acceso a memoria que poseen. En consecuencia, aplicaciones de todo tipo de campos, tales como química, física, ingeniería, inteligencia artificial, ciencia de materiales, etc. que presentan este tipo de patrones de cómputo se ven beneficiadas, reduciendo drásticamente su tiempo de ejecución. En general, el uso de la aceleración del cómputo en GPUs ha significado un paso adelante y una revolución. Sin embargo, no está exento de problemas, tales como problemas de eficiencia energética, baja utilización de las GPUs, altos costes de adquisición y mantenimiento, etc. En esta tesis pretendemos analizar las principales carencias que presentan estos sistemas heterogéneos y proponer soluciones basadas en el uso de la virtualización remota de GPUs. Para ello hemos utilizado la herramienta rCUDA, desarrollada en la Universitat Politècnica de València, ya que multitud de publicaciones la avalan como el framework de virtualización remota de GPUs más avanzado de la actualidad. Los resutados obtenidos en esta tesis muestran que el uso de rCUDA en entornos de Cloud Computing incrementa el grado de libertad del sistema, ya que permite crear instancias virtuales de las GPUs físicas totalmente a medida de las necesidades de cada una de las máquinas virtuales. En entornos HPC (High Performance Computing; Computación de Altas Prestaciones), rCUDA también proporciona un mayor grado de flexibilidad de uso de las GPUs de todo el clúster de cómputo, ya que permite desacoplar totalmente la parte CPU de la parte GPU de las aplicaciones. Además, las GPUs pueden estar en cualquier nodo del clúster, independientemente del nodo en el que se está ejecutando la parte CPU de la aplicación. En general, tanto para Cloud Computing como en el caso de HPC, este mayor grado de flexibilidad se traduce en un aumento hasta 2x de la productividad de todo el sistema al mismo tiempo que se reduce el consumo energético en un 15%. Finalmente, también hemos desarrollado un mecanismo de migración de trabajos de la parte GPU de las aplicaciones que ha sido integrado dentro del framework rCUDA. Este mecanismo de migración ha sido evaluado y los resultados muestran claramente que, a cambio de una pequeña sobrecarga, alrededor de 400 milisegundos, en el tiempo de ejecución de las aplicaciones, es una potente herramienta con la que, de nuevo, aumentar la productividad y reducir el gasto energético del sistema. En resumen, en esta tesis se analizan los principales problemas derivados del uso de las GPUs como aceleradores de cómputo, tanto en entornos HPC como de Cloud Computing, y se demuestra cómo a través del uso del framework rCUDA, estos problemas pueden solucionarse. Además se desarrolla un potente mecanismo de migración de trabajos GPU, que integrado dentro del framework rCUDA, se convierte en una herramienta clave para los futuros planificadores de trabajos en clusters heterogéneos.[CA] En l'última dècada la utilització de la GPGPU(General Purpose computing in Graphics Processing Units; Computació de Propòsit General en Unitats de Processament Gràfic) s'ha tornat extremadament popular en els centres de dades de tot el món. Les GPUs (Graphics Processing Units; Unitats de Processament Gràfic) s'han establert com a elements acceleradors de còmput que s'utilitzen al costat de les CPUs formant sistemes heterogenis. La naturalesa massivament paral·lela de les GPUs, destinades tradicionalment al còmput de gràfics, permet realitzar operacions numèriques amb matrius de dades a gran velocitat degut al gran nombre de nuclis que integren i al gran ample de banda d'accés a memòria que posseeixen. En conseqüència, les aplicacions de tot tipus de camps, com ara química, física, enginyeria, intel·ligència artificial, ciència de materials, etc. que presenten aquest tipus de patrons de còmput es veuen beneficiades reduint dràsticament el seu temps d'execució. En general, l'ús de l'acceleració del còmput en GPUs ha significat un pas endavant i una revolució, però no està exempt de problemes, com ara poden ser problemes d'eficiència energètica, baixa utilització de les GPUs, alts costos d'adquisició i manteniment, etc. En aquesta tesi pretenem analitzar les principals mancances que presenten aquests sistemes heterogenis i proposar solucions basades en l'ús de la virtualització remota de GPUs. Per a això hem utilitzat l'eina rCUDA, desenvolupada a la Universitat Politècnica de València, ja que multitud de publicacions l'avalen com el framework de virtualització remota de GPUs més avançat de l'actualitat. Els resultats obtinguts en aquesta tesi mostren que l'ús de rCUDA en entorns de Cloud Computing incrementa el grau de llibertat del sistema, ja que permet crear instàncies virtuals de les GPUs físiques totalment a mida de les necessitats de cadascuna de les màquines virtuals. En entorns HPC (High Performance Computing; Computació d'Altes Prestacions), rCUDA també proporciona un major grau de flexibilitat en l'ús de les GPUs de tot el clúster de còmput, ja que permet desacoblar totalment la part CPU de la part GPU de les aplicacions. A més, les GPUs poden estar en qualsevol node del clúster, sense importar el node en el qual s'està executant la part CPU de l'aplicació. En general, tant per a Cloud Computing com en el cas del HPC, aquest major grau de flexibilitat es tradueix en un augment fins 2x de la productivitat de tot el sistema al mateix temps que es redueix el consum energètic en aproximadament un 15%. Finalment, també hem desenvolupat un mecanisme de migració de treballs de la part GPU de les aplicacions que ha estat integrat dins del framework rCUDA. Aquest mecanisme de migració ha estat avaluat i els resultats mostren clarament que, a canvi d'una petita sobrecàrrega, al voltant de 400 mil·lisegons, en el temps d'execució de les aplicacions, és una potent eina amb la qual, de nou, augmentar la productivitat i reduir la despesa energètica de sistema. En resum, en aquesta tesi s'analitzen els principals problemes derivats de l'ús de les GPUs com acceleradors de còmput, tant en entorns HPC com de Cloud Computing, i es demostra com a través de l'ús del framework rCUDA, aquests problemes poden solucionar-se. A més es desenvolupa un potent mecanisme de migració de treballs GPU, que integrat dins del framework rCUDA, esdevé una eina clau per als futurs planificadors de treballs en clústers heterogenis.[EN] In the last decade the use of GPGPU (General Purpose computing in Graphics Processing Units) has become extremely popular in data centers around the world. GPUs (Graphics Processing Units) have been established as computational accelerators that are used alongside CPUs to form heterogeneous systems. The massively parallel nature of GPUs, traditionally intended for graphics computing, allows to perform numerical operations with data arrays at high speed. This is achieved thanks to the large number of cores GPUs integrate and the large bandwidth of memory access. Consequently, applications of all kinds of fields, such as chemistry, physics, engineering, artificial intelligence, materials science, and so on, presenting this type of computational patterns are benefited by drastically reducing their execution time. In general, the use of computing acceleration provided by GPUs has meant a step forward and a revolution, but it is not without problems, such as energy efficiency problems, low utilization of GPUs, high acquisition and maintenance costs, etc. In this PhD thesis we aim to analyze the main shortcomings of these heterogeneous systems and propose solutions based on the use of remote GPU virtualization. To that end, we have used the rCUDA middleware, developed at Universitat Politècnica de València. Many publications support rCUDA as the most advanced remote GPU virtualization framework nowadays. The results obtained in this PhD thesis show that the use of rCUDA in Cloud Computing environments increases the degree of freedom of the system, as it allows to create virtual instances of the physical GPUs fully tailored to the needs of each of the virtual machines. In HPC (High Performance Computing) environments, rCUDA also provides a greater degree of flexibility in the use of GPUs throughout the computing cluster, as it allows the CPU part to be completely decoupled from the GPU part of the applications. In addition, GPUs can be on any node in the cluster, regardless of the node on which the CPU part of the application is running. In general, both for Cloud Computing and in the case of HPC, this greater degree of flexibility translates into an up to 2x increase in system-wide throughput while reducing energy consumption by approximately 15%. Finally, we have also developed a job migration mechanism for the GPU part of applications that has been integrated within the rCUDA middleware. This migration mechanism has been evaluated and the results clearly show that, in exchange for a small overhead of about 400 milliseconds in the execution time of the applications, it is a powerful tool with which, again, we can increase productivity and reduce energy foot print of the computing system. In summary, this PhD thesis analyzes the main problems arising from the use of GPUs as computing accelerators, both in HPC and Cloud Computing environments, and demonstrates how thanks to the use of the rCUDA middleware these problems can be addressed. In addition, a powerful GPU job migration mechanism is being developed, which, integrated within the rCUDA framework, becomes a key tool for future job schedulers in heterogeneous clusters.This work jointly supported by the Fundación Séneca (Agencia Regional de Ciencia y Tecnología, Región de Murcia) under grants (20524/PDC/18, 20813/PI/18 and 20988/PI/18) and by the Spanish MEC and European Commission FEDER under grants TIN2015-66972-C5-3-R, TIN2016-78799-P and CTQ2017-87974-R (AEI/FEDER, UE). We also thank NVIDIA for hardware donation under GPU Educational Center 2014-2016 and Research Center 2015-2016. The authors thankfully acknowledge the computer resources at CTE-POWER and the technical support provided by Barcelona Supercomputing Center - Centro Nacional de Supercomputación (RES-BCV-2018-3-0008). Furthermore, researchers from Universitat Politècnica de València are supported by the Generalitat Valenciana under Grant PROMETEO/2017/077. Authors are also grateful for the generous support provided by Mellanox Technologies Inc. Prof. Pradipta Purkayastha, from Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, is acknowledged for kindly providing the initial ligand and DNA structures.Prades Gasulla, J. (2021). Improving Performance and Energy Efficiency of Heterogeneous Systems with rCUDA [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/168081TESISCompendi