Support

NIH-R01-GM61822
NSF-CCR-00-86013

Collaborators

Yih-En Andrew Ban
Paul L. Brown
Herbert Edelsbrunner
Jeffrey J. Headd
Johannes Rudolph

Newsletter Article

The MAPS project was featured in BioGeometry News, April 2005 issue (pdf).

Contact

Comments or requests for the addition of a protein complex to the database: click here.

The majority of intracellular events that affect life-processes are governed by protein-protein interactions. These include, for example, the cellular response to growth factors and hormones via the complex signaling network of protein kinases, phosphatases and G-proteins. We are interested in obtaining a better understanding of protein-protein complex formation by studying the characteristics of known protein complexes. There are no recognized universal rules that characterize these interactions at the molecular level, in contrast to much better understood systems such as gene regulation, enzymatic catalysis, and protein folding. In fact, we can compare the current knowledge of protein-protein interactions with the field of protein structure prior to the creation of the descriptors and classifications that have now become part of the standard language of protein folding. Specifically, the definition of α-helices and ß-sheets and the determination of numerous protein crystal structures made it possible to visualize and classify proteins into families (e.g. β-barrels or β - α - β sandwiches). These classifications provide a set of rules that have led to important insights into protein function, protein folding, protein structure prediction, and evolutionary relationships. In an analogous manner, descriptors of protein interfaces based on composition, shape, and forces would clearly be fundamental to the protein-protein interaction community and provide a better understanding of how life-processes are regulated and how we can manipulate them for the benefit of human health. This website collects, analyzes, and publicizes the discovery, characterization, and visualization of such descriptors of protein interfaces.

Using tools from Computer Science and Mathematics we have defined an interface surface between two or more complexed proteins (Y.-E. A. Ban, H. Edelsbrunner, and J. Rudolph. Interface surfaces for protein-protein complexes. Proceedings of the 8th Annual International Conference on Research in Computational Molecular Biology, 2004, 205-212.). The algorithm and software used to generate the interface surface was created with tools from computational geometry, including weighted Voronoi diagrams, weighted Delaunay triangulations, and topological persistence. Simply described, the interface surface is a wrinkly (non-flat) sheet halfway between two proteins, trimmed where it protrudes beyond the interface. The advantage of working with the interface surface instead of the individual surfaces of interacting proteins is that it provides a single well-defined object that can be readily manipulated in calculations. Importantly, observations and results of further studies can be easily visualized, intuitively describing the nature of protein interfaces and providing insight into existing experimental data.

In our approach, we define a hierarchy of structures on the interface surface, analogous to protein structures. We first define a primary structure that describes the adjacencies of the residues contributing to the interface. These adjacencies can be described both intra- and inter-molecularly at the interface. The primary structure is best visualized in a flattened view. Next we define secondary structures, which are recurring geometric motifs. We believe that most interface surfaces consist of a few canonical motifs (equivalent to α-helices and ß-sheets in protein structures). The landscape of these motifs forms the tertiary structure of an interface. Our goal is to characterize and classify protein interfaces through a deeper understanding of these three hierarchical interface structures as well as their interdependence. We also study a variety of naturally defined functions on the interface surface including the distance to neighboring proteins and electrostatic potentials.