Proteins are biological polymers that fold into specific three-dimensional structures. They are the molecular workhorses of life and are involved in a wide variety of functions such as increasing the rates of chemical reactions, storing and transporting small molecules such as oxygen, mediating the propagation of signals or "instructions" within the cell and much more. Most protein function involves binding to a small molecule or another protein through special features on the surface within so-called binding sites. Dr. Mattos and members of her group are interested in understanding the features that distinguish binding sites on proteins from other areas on the protein surface. This project aims to do this by observing how a variety of small molecules bind to a set of well-studied proteins using a method called X-ray crystallography that allows visualization of the three-dimensional structure of proteins and the associated small molecules at near atomic resolution. The Mattos lab has collected the experimental data sets necessary for this type of analysis and is now using computational methods to mine the data sets for fundamental properties of protein surfaces in general and binding sites in particular. The quantitative methods will be used to validate the correspondence between protein surface properties obtained in the small molecule solvent environment and those observed in the more natural aqueous environment. Once the validation is complete the fundamental protein binding site properties will be directly obtained from experimental data sets acquired in the non-natural solvent environment. Understanding the properties of protein binding sites is critical to understanding of how proteins work and therefore a very important step in making sense of the complicated processes of life.

Broader impact Dr. Mattos has developed this project in such a way that research is an integral part of teaching undergraduates. The research will build on the thriving and diverse educational environment that she has already created in her group. Ten undergraduates from her classes each year will be invited to work with graduate students and the more senior members of the laboratory. The team will participate in an international collaboration with Prof. Janet Thornton's group at the European Bioinformatics Institute (EBI) in England, which is at the forefront of computational analysis of protein experimental databases. Dr. Mattos has recently returned from a sabbatical at the EBI, during which both a graduate and an undergraduate student also participated. She plans to continue to engage students in this international collaboration. In addition, Dr. Mattos is involved in mentoring minority junior faculty members at various universities in the United States and is working to encourage minority undergraduate and graduate students at North Carolina State University to write research proposals for fellowship applications to graduate school.

Agency
National Science Foundation (NSF)
Institute
Division of Molecular and Cellular Biosciences (MCB)
Application #
0818678
Program Officer
Michele McGuirl
Project Start
Project End
Budget Start
2008-08-01
Budget End
2012-04-30
Support Year
Fiscal Year
2008
Total Cost
$576,525
Indirect Cost
Name
North Carolina State University Raleigh
Department
Type
DUNS #
City
Raleigh
State
NC
Country
United States
Zip Code
27695