Alzheimers disease is a disease that causes loss of brain functions that are involved in memory, communication, and thought. The amyloid β-peptide (Aβ has been identified as the core component of protein aggregates in the brain of Alzheimer's patients. The pathway by which Aβ leaves the cell membrane and self-associates is largely a mystery.
The lab of Dr. David Bevan, a faculty member of in the Biochemistry department at Virginia Tech, studies this peptide, with a focus on the association of Aβ with membranes. It is thought that small aggregates of Aβ cause toxicity by disrupting cell membranes. Preventing the formation of these aggregates is an approach that is being studied as way to treat Alzheimer's disease. Experimental work has identified the dietary compounds that may bind to Aβ and inhibit the damaging effects of this peptide.
Part of the challenge is understanding what happens on the molecular level, and it is difficult to apply experimental techniques to find out this mechanism. "It is thought that the onset and the progression of Alzheimer's are due to the aggregation of this particular peptide, and we are trying to understand the molecular mechanisms of the development of the disease," explains Dr. Bevan.
"But with computational methods, we can see at the atomistic level the kinds of interaction and so on. This may lead to changes in the structure of amyloid beta peptide as well as factors that increase the propensity to aggregate."
Computational simulations focus on understanding this effect with the goal of designing effective small molecule inhibitors of Aβ aggregation. The simulations are based on experiments using both in vitro and in vivo studies.
The research in Dr. Bevan' laboratory is focused on molecular modeling as an approach to studying protein structure and function. During the period from January 2011 until May 2012, his lab used 6,000,000 CPU hours on Advanced Research Computing System's (ARC's) now-retired System X supercomputer.
On March 20, 2013, ARC launched a new large-scale machine, BlueRidge, which is comprised of 318 Intel Sandy Bridge nodes. With a total of 5,088 cores and 20 TB of memory, BlueRidge is ARC's largest research computing system to date. Having access to Blue Ridge will help expand Dr. Bevan's research going forward.
He hopes that in some point, his lab will begin to try to simulate the process of protein folding, which takes anywhere from milliseconds to a second depending on the size of the protein and the nature of its folding habit.
"I think with Blue Ridge, we will be able to do that, again by working with fairly small proteins or peptides, especially those that have very distinct protein structure folds, we can simulate the process when they go from extended form into the folded form."
Recently, Dr. Bevan won the award for outstanding dissertation adviser in Science Technology, Engineering, and Mathematics. In addition, his graduate students, Justin Lemkul, a 2012 doctoral degree recipient in Biochemistry, and Nikki Lewis-Huff, a Ph.D. candidate in Bioinformatics and Computational Biology, have received several awards. Anne Brown, another graduate student from his lab, has been accepted into the College of Agriculture and Life Sciences Graduate Teaching Program.
He said that he tries to provide just enough mentoring to his students so they are able to develop their own ideas but do not get totally lost somewhere. "Giving them free reign, so they can conceive and develop their own ideas is important, because they are more enthusiastic about something they have thought about, and they want to see if they can actually perform it, in our case in simulations. When they have generated hypothesis, they want to develop that hypothesis further,"said Dr. Bevan
Other research projects in the Bevan lab are described on the Bevan Lab web site.