Crucial step in AIDS virus maturation simulated for first time

Source: IMIM

Bioinformaticians at IMIM (Hospital del Mar Medical Research Institute) and UPF (Pompeu Fabra University) have used molecular simulation techniques to explain a specific step in the maturation of the HIV virions, i.e., how newly formed inert virus particles become infectious, which is essential in understanding how the virus replicates. These results, which have been published in the latest edition of PNAS, could be crucial to the design of future antiretrovirals.

HIV virions mature and become infectious as a result of the action of a protein called HIV protease. This protein acts like a pair of scissors, cutting the long chain of connected proteins that form HIV into individual proteins that will form the infectious structure of new virions. According to the researchers of the IMIM-UPF computational biophysics group, “One of the most intriguing aspects of the whole HIV maturation process is how free HIV protease, i.e. the ‘scissors protein,’ appears for the first time, since it is also initially part of the long poly-protein chains that make up new HIV virions.

Using ACEMD a software for molecular simulations and a technology known as, Gianni De Fabritiis’ group has demonstrated that the first “scissors proteins” can cut themselves out from within the middle of these poly-protein chains. They do this by binding one of their connected ends (the N-terminus) to their own active site and then cutting the chemical bond that connects them to the rest of the chain. This is the initial step of the whole HIV maturation process. If the HIV protease can be stopped during the maturation process, it will prevent viral particles, or virions, from reaching maturity and, therefore, from becoming infectious.

This work was performed using, a voluntary distributed computing platform that harnesses the processing power of thousands of NVIDIA GPU accelerators from household computers made available by the public for research purposes. It’s akin to accessing a virtual supercomputer. One of the benefits of GPU acceleration is that it provides computing power that is around 10 times higher than that generated by computers based on CPUs alone. It reduces research costs accordingly by providing a level computational power that previously was only available on dedicated, multi-million dollar supercomputers.

Researchers use this computing power to process large numbers of data and generate highly complex molecular simulations. In this specific case, thousands of computer simulations have been carried out, each for hundreds of nanoseconds (billionths of a second) for a total of almost a millisecond.

According to researchers, this discovery in the HIV maturation process provides an alternative approach in the design of future pharmaceutical products based on the use of these new molecular mechanisms. For now, this work provides a greater understanding of a crucial step in the life cycle of HIV, a virus that directly attacks and weakens the human immune system, making it vulnerable to a wide range of infections, and which affects millions of people around the world.


Kinetic characterization of the critical step in HIV-1 protease maturation”. S Kashif Sadiq, Frank Noe and Gianni De Fabritiis. PNAS. DOI:10.1073/pnas.1210983109.

ACEMD Simulation details.

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Penguin Computing Showcases Acellera’s ACEMD at SC2012


Acellera today announced that Penguin Computing will showcase Acellera’s ACEMD on POD (Penguin Computing ON Demand) at Supercomputing 2012 in Salt Lake City, Utah, booth 3866. ACEMD is the world’s fastest and most efficient bio-molecular dynamics (MD) engine for GPU nodes and workstations. Specifically optimized to run on NVIDIA graphics cards, ACEMD enables on a single GPU performance equivalent to more than 100 CPUs while maintaining microsecond trajectories. In combination with POD, ACEMD aims to facilitate the transition of MD from a multi-node, single-trajectory science to high-throughput MD (HT-MD), a new paradigm in computational biophysics.

Matt Jacobs, Sr. Vice President of Corporate Development for Penguin Computing states, “As we approach the clock cycle limits on traditional CPU architectures, multicore and GPU technologies are moving to the forefront to reshape the way our customers conceptualize their research. Acellera’s ACEMD package demonstrates the true capabilities that this new level of parallelism offers and Penguin Computing is pleased to be able to showcase this package on our POD environment at this year’s Supercomputing conference.”

Molecular Dynamics simulation is a powerful technique for investigating biological systems with atomic resolution. Prior to the introduction of Acellera’s ACEMD, the cost of bio-MD simulations for R&D was prohibitive, requiring hundreds of CPU cores for a single run on dedicated HPC clusters. ACEMD transformed the bio-MD field by introducing highly optimized bio-MD simulation on comparatively low-cost GPUs, enabling supercomputing class simulations on a small GPU cluster. ACEMD enables new kinds of analyses, such as the complete reconstruction of protein–ligand interactions in terms of thermodynamics and kinetics, or MD based fragment-based drug discovery. Such studies open new avenues in pharmaceutical research, and illuminate ligand binding site and pose, as well as specific kinetic signatures that can be associated with the quality of small molecules during drug development.

“We are pleased to have this opportunity to work with such a reputable provider of world-class HPC solutions. Penguin’s POD technology combined with Acellera’s ACEMD provides an unbeatable platform for on-demand, highly-efficiency bio-MD simulation for all scientists, from those just beginning to explore its huge potential to established MD users” states Gianni De Fabritiis, Founder and Chief Science Officer at Acellera.

ACEMD is the engine behind GPUGRID, one of the largest distributed computing projects worldwide. ACEMD is stable, scalable, robust, and can handle thousands of highly demanding MD simulations daily. ACEMD simulations have helped researchers push our understanding of protein-ligand interactions, ion channel dynamics, membrane protein behavior, and mechanisms for drug resistance.

Penguin Computing and Acellera are looking to expand their partnership to include turn-key solutions which integrate Acellera and Penguin technology. This would mark Penguin Computing as the first U.S. Value Added Reseller and provider of L1 system support for Metrocubo, Acellera’s MD appliance.

To experience a demonstration of ACEMD at SC2012, visit Penguin Computing booth 1217 November 12-15th where ACEMD simulations will use POD, an HPC cloud that provides instant availability on-demand. Interested parties will be offered the opportunity during those same dates to challenge ACEMD with their own systems on POD. Contact David Soriano at for more information.

About Penguin Computing
For well over a decade Penguin Computing has been dedicated to delivering complete, integrated High Performance Computing (HPC) solutions that are innovative, cost effective and easy to use. Penguin offers a complete end-to-end portfolio of products and solutions ranging from Linux servers and workstations to integrated, turn-key HPC clusters and cluster management software. For users that want to use supercomputing capabilities on-demand and pay as they go, Penguin offers ‘Penguin Computing on Demand’ (POD), a public HPC cloud that is available instantly and as needed. With its broad portfolio of solutions Penguin is the one-stop shop for HPC and enterprise customers and counts some of the world’s most demanding HPC users as its customers, including Caterpillar, Life Technologies, Dolby, Lockheed Martin, the U.S. Air Force, and the U.S. Navy.
To learn more, visit

About Acellera
Acellera is a UK based company focused on providing new technologies in the field of research and development. Since 2006, Acellera has innovated in the field of molecular dynamics simulation software for accelerator processors. Its current flagship product, ACEMD, delivers cluster-computer levels of performance for MD simulations on personal GPU workstations. Computational throughput is also optimized through the joined development of software and hardware. Recently, Acellera designed and patented a new enclosure for GPU optimized calculations for these purposes.
One mission of Acellera is to develop high-throughput molecular dynamics techniques that deliver solutions for estimating common physical chemistry properties as binding affinities, kinetics, poses and pathways with experimental accuracy. The development of new methods for molecular data analysis allows us to understand binding processes to a new level of insight. In this field, the Binding Assay solution by Acellera provides a level of details on the binding process that is unique worldwide.
Acellera is the owner and unique provider of the intellectual property behind all these technologies and the software, hardware infrastructure.
To learn more, visit

Penguin Computing is a registered trademark of Penguin Computing, Inc. Penguin Computing on Demand is a pending trademark in the U.S. ACEMD is a trademark of Acellera. All other trademarks are property of their respective owners. Other product or company names mentioned may be trademarks or trade names of their respective companies.

alejandroPenguin Computing Showcases Acellera’s ACEMD at SC2012
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Acellera will be at SC12 in Salt Lake City NOV 12-15

We will be with Penguin Computing at booth 3866. We will be showcasing ACEMD on POD (Penguin on demand) and also Metrocubo, and the Metrocubo Chassis (Patent Pending). Come see us! Have a system you want to test? Bring the files to the booth and we will benchmark it right there.

alejandroAcellera will be at SC12 in Salt Lake City NOV 12-15
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New paper in JACS on conformational characterization of HIV-1 RT

A new paper using ACEMD has been published in JACS under the title Thumbs Down for HIV: Domain Level Rearrangements Do Occur in the NNRTI-Bound HIV-1 Reverse Transcriptase stemming from a collaboration between University College London (UK) and Universitat Pompeu Fabra (Spain) researchers.

In this work researchers unveiled previously undescribed closed conformations in drug-bound HIV-1 RT which suggesting that “allosteric modulation is effected via the alteration of the kinetic landscape of conformational transitions upon drug-binding”. In the publication researchers also state that “a more detailed understanding of the mechanism of NNRTI inhibition and the effect of binding upon domain motion could aid the design of more effective inhibitors and help identify novel allosteric sites.”

The work was performed through an ensemble molecular dynamics strategy using ACEMD and aggregate simulation time of ~0.6 µs.

D. W. Wright, S. K. Sadiq, G. De Fabritiis, P. V. Coveney, Thumbs Down for HIV: Domain Level Rearrangements Do Occur in the NNRTI-Bound HIV-1 Reverse Transcriptase, J. Am. Chem. Soc., 2012, 134 (31), 12885–12888.

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Science paper confirms ACEMD results

A Science paper titled “Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions” by the group of Professor R. C. Stevens at The Scripps Research Institute in La Jolla, CA (USA) has confirmed the role of sodium ions in the allosteric regulation of GPCRs as it had been modeled by Selent et al. in 2010 using high-throughput MD simulations on ACEMD.

Results by Stevens Group shed on the importance of endogenous small molecules at specific binding sites as control mechanisms of membrane proteins. Such concept exceeds the common view of allostery via pharmacological ligands. The results have profound effects on the current understanding of the functional mechanisms of GPCRs, a broad family of proteins that comprises many of today’s pharmacological targets.

In that regard, computational modeling of small molecule-protein interactions using ACEMD has proven powerful tool to predict unknown solvent-derived effects on protein function.


– Liu W., et al., Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions, Science 2012: 337 (6091), 232-236. DOI:10.1126/science.1219218

– Selent J., et al., Induced Effects of Sodium Ions on Dopaminergic G-Protein Coupled Receptors, PLOS Computational Biology 2010, 6, e1000884. DOI:10.1371/journal.pcbi.1000884

– Source: The Scripps Research Institute

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Acellera Now in North America

We are pleased to inform that Acellera Ltd has now a business development point of contact in North America. Ignasi Buch, a PhD in Computational Biophysics and an experienced user of ACEMD, is based in Pittsburgh, PA (USA). He can be contacted by USA, Canada and Mexico customers for questions regarding any of Acelera’s expanding line high-throughput molecular dynamics based products, as well as for the development of strategic partnerships.

Contact details:
Ignasi Buch, PhD

We look forward to working with you.

The Acellera Ltd. team

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A great new paper using ACEMD

100 for the price of 1:

Current computational tools allow performing microsecond long simulations routinely at low cost.  In a perspective article  Harvey and De Fabritiis discuss in the context of drug discovery the potential of performing molecular dynamics simulations in high-throughput (HT-MD) and argue the time for HT-MD is here.

Sweet dynamics:

Sattelle et al. use ACEMD to produce microsecond simulations of pyranose ring puckering and study its dependence on anomeric configuration. These results appear in the Journal of Physical Chemistry B:

alejandroA great new paper using ACEMD
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