Predictive modelling 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.The new multi-scale protein modelling approach may have implications for an array of biotechnology applications, including bioprocessing and proteomics.
The modelling technique is based on methods previously developed by the same researchers, from the Rensselaer Polytechnic Institute, for predicting the efficacy and side effects of small drug-like molecules.
In tests performed by the scientists, 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.
"The ability to predict the separation behaviour 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 modelling approach can be used to determine protein behaviour 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," he added.
The team intend to test the model against more complicated protein structures as part of its further development. The outcome of this work will yield fundamental information about the complex relationship between a protein's structural features and its chemical binding properties, aiding in evaluating its potential in biomedical applications.
The research findings are reported in the Aug. 16 issue of Proceedings of the National Academy of Sciences, titled: "A Priori Prediction of Adsorption Isotherm Parameters and Chromatographic Behaviour in Ion-Exchange Systems."