Efficient large-scale replica-exchange simulations on production infrastructure

Thota, Abhinav; Luckow, André; Jha, Shantenu

doi:10.1098/rsta.2011.0151

Cited by 11 publications

(8 citation statements)

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“…15 This enables the efficient execution of a range of replica exchange schemes. An early prototype of the software system used for performing current simulations using the current asynchronous protocol has been described in Ref.…”

Section: Methodsmentioning

confidence: 99%

Characterization of the Three-Dimensional Free Energy Manifold for the Uracil Ribonucleoside from Asynchronous Replica Exchange Simulations

Radak

Romanus

et al. 2015

J. Chem. Theory Comput.

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Replica exchange molecular dynamics has emerged as a powerful tool for efficiently sampling free energy landscapes for conformational and chemical transitions. However, daunting challenges remain in efficiently getting such simulations to scale to the very large number of replicas required to address problems in state spaces beyond two dimensions. The development of enabling technology to carry out such simulations is in its infancy, and thus it remains an open question as to which applications demand extension into higher dimensions. In the present work, we explore this problem space by applying asynchronous Hamiltonian replica exchange molecular dynamics with a combined quantum mechanical/molecular mechanical potential to explore the conformational space for a simpleribonucleoside , using a newly developed software framework capable of executing >3,000 replicas with only enough resources to run 2,000 simultaneously, which may not be possible with traditional synchronous replica exchange approaches. Our results demonstrate 1.) the necessity of high dimensional sampling simulations for biological systems, even as simple as as a single ribonucleoside, 2.) the utility of asynchronous exchange protocols in managing simultaneous resource requirements expected in high dimensional sampling simulations. It is expected that more complicated systems will only increase in computational demand and complexity and thus the reported asynchronous approach may be increasingly beneficial in order to make such applications available to a broad range of computational scientists.

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Section: Methodsmentioning

confidence: 99%

Characterization of the Three-Dimensional Free Energy Manifold for the Uracil Ribonucleoside from Asynchronous Replica Exchange Simulations

Radak

Romanus

et al. 2015

J. Chem. Theory Comput.

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“…One example is a SAGA-based Pilot-Job called BigJob [23], which provides the ability to run multiple concurrent large-scale simulations; the advert-service provides the coordination capabilities, and can be used to manage more complicated coordinated workflows (for example replica exchange or ensemble methods with interdependent ensemble members). As shown in [12,13], this approach can be used to scale-out to hundreds of replicas/ensemble-members over multiple supercomputers concurrently.…”

Section: Saga and Bigjobmentioning

confidence: 98%

“…This is a common problem in high throughput computing (HTC), in that the requirement is to optimise the time to completion of a bag of tasks rather than the run time of any individual job. The infrastructure utilised in this study provides a general model that could also be used to facilitate simulation techniques in which some level of coupling between different simulations, such as replica exchange molecular modelling [12,13], is involved.…”

Section: Introductionmentioning

confidence: 99%

Towards high-throughput, high-performance computational estimation of binding affinities for patient specific HIV-1 protease sequences

Kenway

Wright

Heller

et al. 2011

Proceedings of the 2011 TeraGrid Conference: Extreme Digital Discovery

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The rapid acquisition of mutations conferring resistance to particular drugs remains a significant cause of anti-HIV treatment failure. Informatics based techniques give resistance scores to individual mutations which can be combined additively to assess the resistance levels of complete sequences. It is likely however, that the full picture is more complicated, with non-linear epistatic effects between combinations of mutations playing an important role in determining the level of viral resistance [1,2]. Molecular dynamics is one simulation technique which offers the ability to derive quantitative (as well as qualitative) insight into the interplay of resistance-causing mutations. The dynamics of sequence specific models can be simulated and the free energy change associated with the drug binding calculated. The free energy change (or binding affinity) is the thermodynamic quantity which determines how tightly a drug will bind to its target. Hence, comparing values for mutant and wildtype systems allows the level of resistance of a particular sequence to be estimated. Validating such an approach is computationally demanding and the management of large numbers of simulations is a considerable administrative challenge. Here we present the use of tools based on the Simple API for Grid Applications (SAGA) to tackle this computational problem. This allows us to utilise high-end infrastructure, such as TeraGrid/XD, to provide extreme scales of throughput for highperformance simulations. This paper presents initial results and experience of using the TeraGrid in conjunction with DEISA, the European analogue of the US TeraGrid. Highthroughput (high-performance) calculations are one of the few classes of computational problems that can easily exploit the computational power of widely distributed computing resources, thereby amassing more computational power than any of the individual resources could offer. In addition to the resource utilization rationale the need for cross-Grid capabilities in this case arises from shared and complementary scientific and technical skills found in this intercontinental collaboration.

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“…A metric for the simplicity of the model is the number of elements of the model, which is very low with four main concepts. The design of the pilot-abstraction Pilot-Job [63], [6] Pilot-Data [66] Pilot-Hadoop [67] Pilot-Memory [ Conceptual model [6], architecture model [63] Conceptual model [6], architecture model [66] Architecture model [67] Architecture model [68] Architecture model [32] Performance Adaptive Replica Exchange [48], [72], Ensemble Kalman Filter simulations [50], HIV binding [49], science portals [51], Pilot-MapReduce [54] Genome Sequencing, K-Mean [66], [55] Wordcount, K-Means K-Means Light source data reconstruction, K-Means…”

Section: A Problem Identification and Design Evaluation (Eval 1/2)mentioning

confidence: 99%

Methods and Experiences for Developing Abstractions for Data-intensive, Scientific Applications

Luckow¹,

Jha²

2020

Preprint

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Developing software for scientific applications that require the integration of diverse types of computing, instruments, and data present challenges that are distinct from commercial software. These applications require scale, and the need to integrate various programming and computational models with evolving and heterogeneous infrastructure. Pervasive and effective abstractions for distributed infrastructures are thus critical; however, the process of developing abstractions for scientific applications and infrastructures is not well understood. While theory-based approaches for system development are suited for well-defined, closed environments, they have severe limitations for designing abstractions for scientific systems and applications. The design science research (DSR) method provides the basis for designing practical systems that can handle real-world complexities at all levels. In contrast to theory-centric approaches, DSR emphasizes both practical relevance and knowledge creation by building and rigorously evaluating all artifacts. We show how DSR provides a well-defined framework for developing abstractions and middleware systems for distributed systems. Specifically, we address the critical problem of distributed resource management on heterogeneous infrastructure over a dynamic range of scales, a challenge that currently limits many scientific applications. We use the pilot-abstraction, a widely used resource management abstraction for high-performance, high throughput, big data, and streaming applications, as a case study for evaluating the DSR activities. For this purpose, we analyze the research process and artifacts produced during the design and evaluation of the pilot-abstraction. We find DSR provides a concise framework for iteratively designing and evaluating systems. Finally, we capture our experiences and formulate different lessons learned.

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Efficient large-scale replica-exchange simulations on production infrastructure

Cited by 11 publications

References 10 publications

Characterization of the Three-Dimensional Free Energy Manifold for the Uracil Ribonucleoside from Asynchronous Replica Exchange Simulations

Characterization of the Three-Dimensional Free Energy Manifold for the Uracil Ribonucleoside from Asynchronous Replica Exchange Simulations

Towards high-throughput, high-performance computational estimation of binding affinities for patient specific HIV-1 protease sequences

Methods and Experiences for Developing Abstractions for Data-intensive, Scientific Applications

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