CAPTION Simulation of BRD4 interacting with a potent inhibitor. CREDIT Image courtesy of Dr. Bradley Dickson, Rothbart Laboratory, Van Andel Research Institute.

A new computational tool called fABMACS is helping scientists see beyond static images of proteins to more efficiently understand how these molecules function, which could ultimately speed up the drug discovery process.

Proteins are the molecular workhorses of biology--they carry out the instructions written in the genetic code. Their shape plays a crucial role in their function and their ability to interact with other molecules. Scientists study these interactions to develop new insights into protein function and to develop targeted therapies for diseases such as cancer.

"The goal of targeted drug design is to create a molecule that interacts specifically with a protein, and this requires a description of protein-drug interactions that is precise--down to the placement of each atom," said Bradley Dickson, Ph.D., a computational biophysicist in the laboratory of Scott Rothbart, Ph.D., at Van Andel Research Institute (VARI)and first author of a paper describing the tool. "The creation of fABMACS is a significant step toward robust virtual drug discovery because it saves time and money. It allows us to better harness the power of existing software while greatly improving our ability to predict the way that a potential drug interacts with a protein."

Scientists often rely on collecting snapshots of proteins to determine how they may interact with a potential drug. However, these images are static and do not depict changes in proteins' shape.

"These snapshots provide valuable insight that can be enriched by fABMACS," said Rothbart, assistant professor at VARI and the study's senior author. "fABMACS allows us to simulate chemical changes to the drug and more quickly predict how those changes impact its interaction with the target protein. Ultimately, this could translate to improved drug potency and efficacy."

To demonstrate the tool's capabilities, the team ran several accelerated supercomputer simulations of the epigenetic regulatory protein BRD4 bound to a drug that is currently in phase I clinical trials for blood cancers. They demonstrated that a slight change to the compound's chemical structure could improve binding to its target protein, thereby improving its effect. The results of this work were published recently in the Journal of Chemical Physics.

Fast, stable and scalable

fABMACS is an add-on to existing molecular dynamics software. It is based on GROMACSv5.0.5 and optimizes network communication and load balancing--both critical aspects of software development in parallel computing environments--to achieve a low-overhead implementation of new free-energy techniques. fABMACS also comes with a built-in configuration tool that allows the code to be tailored to different applications without requiring the user to manually edit the code, which maximizes transferability.

As part of a grant from the National Science Foundation, FIU and two other Florida universities will receive $1 million each in student scholarships to remove financial barriers to student success and increase the number of graduates in computer and information technology.

The scholarships are part of a $5 million, five-year grant awarded to FIU and its partners, the University of South Florida and the University of Central Florida, in support of the collaborative Florida IT Pathways to Success project. The goals of the project, which build on a previously awarded TEAm Grant from the Florida Board of Governors, include recruiting, retaining, and providing scholarships and other support to academically talented students in IT-related disciplines, who have financial need. Located in Florida'sthree largest metropolitan areas, the three institutions comprise the Florida Consortium of Metropolitan Research Universities. Collectively these universities serve about half of the students and produce about 65 percent of the IT graduates in the State University System.

Historically, science, technology, engineering and mathematics – or STEM – degrees take longer to finish than other majors. In some cases, students run out of financial aid before they are able to graduate. With this in mind, some of the scholarships are aimed at preventing students who are close to completing their degrees from being derailed by financial pressures.

"This grant will support our commitment to those students at risk of dropping out of college when they are within striking distance of graduation," said the principal investigator of the grant, Mark Weiss, associate director for academic affairs at the School of Computing and Information Sciences, within the FIU College of Engineering and Computing.

Funds from the grant will support each institution's ongoing efforts to align degrees with the state's workforce needs.

"This grant will allow us to empower students to pursue computer science degrees and help prepare them for careers in these high-demand areas," said co-principal investigator, Zahra Hazari of the STEM Transformation Institute and Department of Teaching and Learning in the FIU College of Arts, Sciences & Education.

Computer science has been positioned as an emerging critical discipline for American students. Last year, there were more than 600,000 high-paying tech jobs in the United States and not enough people to fill them. By 2018, it's projected that 51 percent of all STEM jobs will be in computer science-related fields.

STEM is an important part of FIU's contribution to workforce preparation, innovation and research for Florida and the nation. The College of Engineering and Computing accounted for 56 percent of FIU's STEM degrees in the last academic year, with more than 400 of those graduating with a degree in computer science or information technology.

Shuchin Aeron, assistant professor of electrical and computer engineering in Tufts University's School of Engineering, has received a Faculty Early Career Development (CAREER) award from the National Science Foundation (NSF) and U.S. Department of Energy. Shuchin is the fourth member of the School of Engineering faculty this year to be recognized as one of the country's most promising scientists and engineers. 

Aeron received a five-year $530,000 NSF award for his work advancing multidimensional data science via new algebraic models and algorithms. He aims to re-invigorate interest among other researchers in using tools from linear and multilinear algebra that are currently overlooked. 

The new algorithms can be applied to problems in a wide range of fields, including social networks, medical imaging, geophysical inversion, computer vision, big data management, and forecasting of complex events. As a result, the research involves collaboration with multiple groups at Tufts and beyond, including: the Department of Mathematics in the School of Arts & Sciences, the Department of Neuroscience in the School of Medicine, and the Tufts Interactive Learning and Collaboration Environment (InterLACE) program, part of the School of Engineering's Center for Engineering Education and Outreach; Brigham and Women's Hospital in Boston; and AT&T.

"Shuchin is an example of the depth and breadth of talented researchers within our engineering faculty who are investigating fresh approaches to fundamental challenges. His work holds great promise for his field," said Jianmin Qu, dean of the School of Engineering.

Earlier this year, the NSF recognized three other School of Engineering faculty members, including:

  • Kristen Bethke Wendell, assistant professor of mechanical engineering, who received the Presidential Early Career Award for Scientists and Engineers, the highest U.S.-sponsored honor given to science and engineering professionals in the early stages of their independent research careers. Her five-year, $600,000 award will support a research project that seeks to develop, implement, and assess a model that introduces novice elementary school teachers to community-based engineering design as a strategy for teaching and learning in urban schools.
  • Ayse Asatekin, assistant professor of chemical and biological engineering and director of the Smart Polymers, Membranes and Separations Laboratory, who received a five-year $500,000 early career award to build a research and education plan centered on developing novel membranes with new capabilities by designing polymers that self-assemble to form nanostructures.
  • Jeffrey Guasto, assistant professor of mechanical engineering and director of the Microscale Mechanics and Transport in Biological Systems Laboratory, who received a five-year $500,000 early career award for his investigation of how material properties of viscous fluids affect the motion of cells.

Tufts University, located on three Massachusetts campuses in Boston, Medford/Somerville, and Grafton, and in Talloires, France, is recognized among the premier research universities in the United States. Tufts enjoys a global reputation for academic excellence and for the preparation of students as leaders in a wide range of professions. A growing number of innovative teaching and research initiatives span all campuses, and collaboration among the faculty and students in the undergraduate, graduate and professional programs across the university is widely encouraged.

Striving to address societal challenges in sectors including Health, Energy and the Environment, the European Union is developing the European Open Science Cloud, a complete socio-technical environment, including robust e-infrastructures capable of providing data and computational solutions where publicly funded research data are Findable, Accessible, Interoperable and Re-usable (FAIR).

Since 2007 The European Commission (EC) has invested more than €740 million in e-infrastructures through Horizon 2020 (the European Union Research and Innovation programme 2014-2020) and FP7 (the European Union's Seventh Framework Programme for Research and Technological Development). They want to see this exploited in full.

Many research communities are, however, struggling to benefit from this investment. The authors call for greater emphasis on Virtual Research Environments (VREs) as the only way for researchers to capitalise on EC advances in networking and supercomputing. The authors characterise this as a "last mile" problem, a term borrowed from telecommunications networks and once coined to emphasise the importance (and difficulty) of connecting the broader network to each customer's home or office. Without the last mile of connectivity, a network won't generate a cent of value.

Some concerns around the transition to Open Digital Science refer to attribution and quality assurance, as well as limited awareness of open science and its implications to research. However, most difficulties relate to many e-infrastructure services being too technical for most users, not providing easy-to-use interfaces and not easily integrated into the majority of day-to-day research practices.

Trustworthy and interoperable Virtual Research Environments (VREs) are layers of software that hide technical details and facilitate communication between scientists and computer infrastructures. They serve as friendly environments for the scientists to work with complicated computer infrastructures, while being able to use their own set of concepts, ways of doing things and working protocols.

Helping them to solve the difficulties noted above, VREs could guide the skeptical research communities along the 'last mile' towards Open Digital Science, according to an international team of scientists who have published their Policy Brief in the open access journal Research Ideas and Outcomes (RIO).

The authors state "These domain-specific solutions can support communities in gradually bridging technical and socio-cultural gaps between traditional and open digital science practice, better diffusing the benefits of European e-infrastructures". They also recognise that "different e-infrastructure audiences require different approaches."

"Intuitive user interface experience, seamless data ingestion, and collaboration capabilities are among the features that could empower users to better engage with provided services," stress the authors.

Goldenchip

 An image of a gold chip used to trap ions for use in quantum supercomputing has won the overall prize in a national science photography competition, organised by the Engineering and Physical Sciences Research Council (EPSRC). 

'Microwave ion-trap chip for quantum computation', by Diana Prado Lopes Aude Craik and Norbert Linke, from the University of Oxford, shows the chip's gold wire-bonds connected to electrodes which transmit electric fields to trap single atomic ions a mere 100 microns above the device's surface. 

The image, taken through a microscope in one of the university's cleanrooms, came first in the Eureka category as well as winning overall against many other stunning pictures, featuring research in action, in the EPSRC competition - now in its third year. 

Doctoral student Diana Prado Lopes Aude Craik, explained how the chip works: "When electric potentials are applied to the chip's gold electrodes, single atomic ions can be trapped. These ions are used as quantum bits ('qubits'), units which store and process information in a quantum computer. Two energy states of the ions act as the '0' and '1' states of these qubits. Slotted electrodes on the chip deliver microwave radiation to the ions, allowing us to manipulate the stored quantum information by exciting transitions between the '0' and '1' energy states. 

"This device was micro-fabricated using photolithography, a technique similar to photographic film development. Gold wire-bonds connect the electrodes to pads around the device through which signals can be applied. You can see the wire-bonding needle in the top-left corner of the image. The Oxford team recently achieved the world's highest-performing qubits and quantum logic operations."

The development of the ion-trap chip was funded jointly by the EPSRC and the US Army Research Office.

The competition's five categories were: Eureka, Equipment, People, Innovation, and Weird and Wonderful. Winning images feature:

  • A spectacular 9.5 metre wave created to wow crowds at the FloWave Ocean Energy Research Facility at the University of Edinburgh
  • An iCub humanoid robot learning about how to play from a baby as part of robotics research taking place at Aberystwyth University
  • The intense, blinding light of plasma formed by an ultrafast laser being used to process glass at the EPSRC Centre for Innovative Manufacturing in Ultra Precision at the University of Cambridge
  • A beautiful rotating jet of viscoelastic liquid water resembling a spinning dancer that demonstrates the effect of adding a tiny amount of polymer to water and an example of fluid dynamics research at Imperial College London 

One of the judges was Professor Robert Winston, he said: "It is crucial to promote greater understanding of science and engineering research, the role it plays in making new discoveries, developing new technologies and in making the world a better place for us all. These are truly inspirational images and tell great stories. It was a real pleasure to take part as a judge and I hope people will want to find out more."

Congratulating the winners and entrants, Professor Philip Nelson, EPSRC's Chief Executive, said: "Yet again, the standard of entries into this year's competition shows the inquisitive, artistic and perceptive nature of the people EPSRC supports. I'd like to thank everyone who entered; you made judging a very hard but enjoyable task.

"This competition helps us engage with academics and these stunning images are a great way to connect the general public with research they fund, and inspire everyone to take an interest in science and engineering." 

The competition received over 200 entries which were drawn from researchers in receipt of EPSRC funding. 

The judges were: 

Martin Keene - Group Picture Editor - Press Association; 
Professor Robert Winston - Professor of Science and Society and Emeritus Professor of Fertility Studies at Imperial College London 
Professor Philip Nelson - EPSRC's Chief Executive 

The first, second and third prize winning images with descriptions are all available to download from the EPSRC website http://www.epsrc.ac.uk

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