"Predictive modeling is a new approach to drug discovery that takes information from lab analysis and concentrates it in predictive models that may be evaluated on a computer," said Curt M. Breneman, professor of chemistry and chemical biology at Rensselaer.
"The ability to predict the separation behavior of a particular protein directly from its structure has considerable implications for biotechnology processes," said Steven Cramer, professor of chemical and biological engineering at Rensselaer. "The research results thus far indicate that this modeling approach can be used to determine protein behavior for use in bioseparation applications, such as the protein purification methods used in drug discovery. This could potentially reduce the development time required to bring biopharmaceuticals to market."
The modeling technique is based on methods previously developed by Breneman's group for rapidly predicting the efficacy and side effects of small drug-like molecules. The newly developed model successfully predicted the amount of a protein that binds to a material under a range of conditions by using molecular information obtained from the protein structure. These predicted adsorption isotherm parameters then replicated experimental results by predicting the actual separation profile of proteins in chromatographic columns. Chromatography techniques are used to identify and purify molecules, in this case, particular proteins.
"We intend to test the model against more complicated protein structures as part of its further development," said Breneman. "The outcome of this work will yield fundamental information about the complex relationship between a protein's structural features and its chemical binding properties, and also aid in evaluating its potential biomedical applications."
The research findings are reported in the Aug. 16 issue of Proceedings of the National Academy of Sciences in a paper titled "A Priori Prediction of Adsorption Isotherm Parameters and Chromatographic Behavior in Ion-Exchange Systems."
In addition to Breneman and Cramer, the collaborative research team includes Asif Ladiwala and Kaushal Rege, who both recently earned doctorates in chemical and biological engineering at Rensselaer. The work was supported by the National Science Foundation and GE Healthcare.
The researchers' computational model uses a combination of molecular-level quantitative structure-property relationship models with macroscopic steric mass action isotherm models and support vector machine regression computations.
Biotechnology and Interdisciplinary Studies at Rensselaer
At Rensselaer, faculty and students in diverse academic and research disciplines are collaborating at the intersection of the life sciences and engineering to encourage discovery and innovation. Rensselaer's four biotechnology research constellations - biocatalysis and metabolic engineering, functional tissue engineering and regenerative medicine, biocomputation and bioinformatics, and integrative systems biology - engage a multidisciplinary mix of faculty and students focused on the application of engineering and physical and information sciences to the life sciences. Ranked among the world's most advanced research facilities, Rensselaer's Center for Biotechnology and Interdisciplinary Studies provides a state-of-the-art platform for collaborative research and world-class programs and symposia.
Rensselaer Polytechnic Institute, founded in 1824, is the nation's oldest technological university. The university offers bachelor's, master's, and doctoral degrees in engineering, the sciences, information technology, architecture, management, and the humanities and social sciences. Institute programs serve undergraduates, graduate students, and working professionals around the world. Rensselaer faculty are known for pre-eminence in research conducted in a wide range of fields, with particular emphasis in biotechnology, nanotechnology, information technology, and the media arts and technology. The Institute is well known for its success in the transfer of technology from the laboratory to the marketplace so that new discoveries and inventions benefit human life, protect the environment, and strengthen economic development.