UAB Synopsis, Vol. 24, No. 19, May 23, 2005
Campus-wide effort focuses on structure of living systems
With expertise from scientists in diverse disciplines, including medicine, microbiology, mathematics, physics, engineering, and chemistry, UAB's Center for Computational and Structural Biology (CCSB) brings together computer-intensive, structure-based approaches aimed at uncovering functional and interactive mechanisms of complex living systems, Professor of Medicine and CCSB Director Jere Segrest, MD, PhD, says.
"The center is combining powerful tools — X-ray crystallography, nuclear magnetic resonance spectroscopy, cryo-electron microscopy, and computational biology — to develop detailed molecular models of a gene's protein products. Structural images can tell us how proteins function and interact in health and disease and will foster rational drug design," he says.
Dr. Segrest and Director of UAB's Center for Biophysical Sciences and Engineering Larry DeLucas, OD, PhD, who is contributing X-ray crystallography expertise to CCSB, share an interest in determining membrane protein structures.
"Half of all therapeutic drugs target membrane proteins, but only about 20 of 300,000 have been crystallized, so we know very little about their structure," Dr. Segrest says. "Computational biology, which uses the linked power of high-performance computers to mimic movements of individual molecules, is poised to give us meaningful information about membrane proteins, predicting their structure and telling us how they interact with each other."
Dr. Segrest cites cystic fibrosis transmembrane regulator (CFTR), the protein defective in cystic fibrosis, as an example of a membrane protein of interest at UAB whose structure could be predicted by computational biology. "The crystallography group has been working to crystallize CFTR but has not yet determined its structure. Creating predictive computer models of CFTR could provide clues that ultimately lead to its crystallization."
UAB's Enabling Technology Laboratory (ETL) in the Department of Mechanical Engineering provides the massive computing power required by such modeling. ETL's cluster of 124 high-performance computers will increase to 512 in the next few months, Dr. Segrest says.
Trans-campus Effort
Professor of Microbiology Peter Prevelige, PhD, is CCSB associate director. His work focuses on hydrogen deuterium exchange, which can help quantify protein structure changes and is part of the center's efforts to develop methods of mapping protein-lipid interactions, Dr. Segrest says.
"The center coordinates UAB's efforts in structural biology, bringing together scientists from the medical and academic sides of the campus," says Dr. Segrest, who gives credit to the CCSB's influential "trans-institutional" advisory committee for helping make the center possible.
Committee members include Drs. DeLucas and Prevelige, Vice President for Research Richard Marchase, PhD; Dean of the School of Engineering Linda Lucas, PhD; Dean of the School of Natural Sciences and Mathematics Lowell Wenger, PhD; Associate Dean of Medicine Samuel Brown, EdD; Department Chairs David Chaplin, MD, PhD, microbiology; David Graves, PhD, chemistry; William Koopman, MD, medicine; Jay M. McDonald, MD, pathology; David Shealy, PhD, physics; Anthony Skjellum, PhD, computer and information sciences, Bharat Soni, PhD, mechanical engineering; and Tim M. Townes, PhD, biochemistry and molecular genetics.
"Combining different approaches to solve the extremely complex problems of structural biology can lead to extraordinary new drugs and procedures targeting humans' most persistent and difficult medical problems," Dr. Segrest says.
"Ultimately, the answers to the questions we ask could tell us everything we want to know about living organisms, wellness, treatment of disease, and aging."