Temple Magazine

Remote Control

The Institute for Computational Molecular Science makes formerly unfathomable experimentation possible.

Story by Brian M. Schleter

Throughout history, the greatest scientific and engineering advances have resulted from theories proven through costly, sometimes dangerous and often repetitive forms of experimentation.

Advances in computer technology are changing that dynamic—rapidly. Every day, researchers use high-performance computers, capable of performing quadrillions of calculations per second, to design safer, more effective medicines; predict the effects of climate change; and search for new treatments for HIV, influenza and other diseases.

Increasingly, researchers in the natural and life sciences are turning to computational science to observe video simulations of molecular activity. Now, researchers at Temple can utilize the Institute for Computational Molecular Science (ICMS) in the College of Science and Technology.

ICMS was founded in 2009 by Laura H. Carnell Professor of Science Michael Klein, member of the esteemed National Academy of Sciences—one of the highest honors bestowed on a scientist—author of more than 600 publications, editor of four books and winner of the American Physical Society’s Aneesur Rahman prize for outstanding computational research.

A leader in his field, Klein aims to bring Temple’s research to the forefront of science and to foster cross-disciplinary team-building through ICMS, a new valuable tool for generating new approaches to discovery of all kinds.

From increasing research capabilities for students to allowing scientists to witness molecular interaction visually, ICMS’s computing will push the boundaries of what can be accomplished—and what can be understood—at Temple.

“Computational science is commonly described as the third pillar of scientific discovery, beside theory and experimentation,” says Axel Kohlmeyer, associate director of ICMS and associate research professor at Temple. “We use computers to do experiments that cannot be done in reality.”

Building Bridges

In today’s research landscape, anyone who needs a quick answer or has a large block of data to process needs high-performance computing. Within ICMS, a dozen Temple chemists, biochemists, physicists and computer scientists use state-of-the-art computer simulations to model molecular behaviors. Similar to the way video games simulate experiences based on data —but on a much more expansive and complex level—computer models designed by the ICMS group utilize scientific data to verify the results of experiments put forth by collaborating researchers.

“Providing high-performance computing tools is a bit like being a pipefitter,” Kohlmeyer says. “There is a certain infrastructure that has to be available and maintained. If you pull a certain handle, you’ll get hot water. People without that knowledge, working by themselves, wouldn’t be able to get hot water.”

Klein, a 16-year member of the chemistry faculty and director of the Center for Molecular Modeling at the University of Pennsylvania, came to Temple to found ICMS. That decision played a role in Robert Kulathinal’s decision to join the faculty last year.

“Temple’s successful recruitment of the ICMS group was exemplary of the university’s commitment to both innovation and excellence,” says Kulathinal, an evolutionary geneticist and assistant professor of biology. “It confirmed that this is a place I wanted to be.”

His lab plans to use ICMS’s extraordinary computing resources to construct three-dimensional protein models from genome sequence data, to understand how proteins have evolved over millions of years. Kulathinal says the modeling might lead to a new understanding of how proteins interact, resulting in more effective drug treatments.

Part of Klein’s strategy is to seek seed funding for researchers to collaborate across disciplines. An example, he says, would be a pharmacologist working to develop a new compound who needs a chemist to synthesize it.

Klein and Kohlmeyer

ICMS Director Michael Klein (right) and ICMS Associate Directo Axel Kohlmeyer are redefining research at Temple. Photo courtesy Joseph V. Labolito.

molecule

A C_60 molecule (or “buckyball”) is swallowed by a bilayer of lipid molecules, a model for a cell membrane. Researchers study if the otherwise inert buckyballs can have negative effects on cell membranes. Image courtesy of ICMS.

The role of the ICMS would be to use computers to help in the screening of millions of possible molecules to find potential targets and thus reduce the workload of the synthetic chemist. By facilitating these conversations, the ICMS is creating an environment where “random, unexpected collisions” of this sort can occur.“ We’re trying to build bridges,” Klein says.

Providing the Tools

Though the work of ICMS encompasses an array of different sciences and researchers, the common theme in all of the institute’s projects is the smart and effective use of high-performance computing clusters, or HPC clusters.

Just as bridges need sturdy foundations, the first order of business for ICMS is to build a state-of-the-art cyberinfrastructure at Temple. The university now has a hybrid GPU (graphics processing unit)/CPU (central processing unit) cluster computer.

In Temple’s case, the HPC cluster features more than 100 nodes containing more than 1,200 processor cores, 48 Nvidia Tesla GPUs (hardware made specifically for high-perfomance computing) and 120 terabytes of storage.

In other words, the HPC cluster is the equivalent of hooking up approximately 2,000 laptop computers set to process the same information. It provides more hard-drive space than 240 computers that each contain a 500-gigabyte hard drive.

Beyond the astounding capacity of the HPC cluster at Temple, ICMS also is part of TeraGrid, a cyberinfrastructure of even more powerful supercomputers used for scientific research, information and data sharing, which not only encourages cross-disciplinary research, but also fosters collaboration between Temple and other TeraGrid researchers across the country.

Targeting the Impossible

Most of the ICMS group’s research is literally “trying to do the impossible,” Kohlmeyer notes, by putting theoretical models to the test. Because simulations are numbers-based, they know the exact state of the whole system at any point, allowing for perfectly controlled experiments.

The institute’s ultimate goal—Kohlmeyer calls it the “holy grail” of computational science—is to arrive at a juncture where the molecular computer simulations built are so accurate and detailed, they render many chemical and biological experiments obsolete. Imagine a scenario in which a new drug is proven safe and effective outside the laboratory—where it currently takes years of high-cost testing—and on a computer instead, with every possible molecular interaction taken into account.

Though the technology is not there yet, much of the current research at ICMS is helping researchers improve drug treatments.

For example, one team is looking at the cellular binding abilities of certain anesthesia agents.“We know that anesthetics work, but we don’t know how they work on the molecular level,” Kohlmeyer explains. Understanding the molecular activity of anesthetic agents, he says, will result in safer anesthetics that can better target the area of the body they are meant to act upon.

Polymer chemists in the group are using computer simulations to unlock the secrets of nano-scale materials. Mixing multiple polymers (chemical compounds) and studying the new mixture that arises on the nano level can improve drug delivery. “The purpose is to ‘package’ a drug so it can get where it needs to be, instead of ‘flooding’ the body and thus risking side effects,” Kohlmeyer explains.

Another area of focus at ICMS is software development. Last summer, Kohlmeyer supervised two undergraduate students who helped improve a simulation software package. The effect enabled a postdoctoral researcher to run his calculations up to 15 times faster than before, greatly improving the researcher’s efficiency.

“As I see it, the mission of ICMS, in this context, is to share our experiences with other Temple researchers and, in return, learn from their experiences,” Kohlmeyer says. “Ultimately, we want to establish collaborative efforts that can solve even more complex problems than the ones being worked on now.”

As ICMS grows, so too will opportunities for groundbreaking research at Temple.

“The vision for this institute is to foster collaborative, interdisciplinary, frontier research,” Klein says. “It will take time, but it will be driven largely by recruitment. We need to recruit people aggressively at all levels to staff centers and institutes, especially young people. This new generation of researchers is more adept at using computers to solve complex problems.”

Brian M. Schleter is a research freelance writer based in Baltimore City, Md.

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