The Molecular Modeling Facility (MMF) provides state-of-the-art services in protein sequence analysis and structure prediction to Fox Chase Cancer Center (FCCC) investigators. These services include database searches, multiple sequence alignments, phylogenetic tree comparisons, secondary structure predictions, transmembrane, coiled-coil and disordered region predictions, homology modeling of single proteins and complexes, protein-protein and protein-ligand docking, and ligand design. The Facility has been operating since 2003, and was approved as a CCSG resource at the last review. Currently, at least one-half of sequenced proteins are homologous at least in part to a protein of known structure. Homology modeling methods use known structures to build three-dimensional models of target proteins and protein complexes of unknown structure. These models can be used to predict functional interactions with other molecules, to explain existing experimental data, to generate testable hypotheses, and in some cases to become the basis for design of specific inhibitors for translational research. The Facility has performed services for 48 principal investigators with peer-reviewed funding in all five Research Programs since 2005. The Facility and the Facility Director's research group have developed new software for automating the modeling process to allow Facility staff more time to concentrate on the biological problem under study. In particular, they have developed methods for predicting the structures of protein homo- and heterooligomers, which comprise many important functional interactions. This software is extensible, so that it allows new tools to be incorporated into the same graphical user interface as they become available. As technologies such as two-hybrid interaction mapping and two-dimensional gel electrophoresis allow investigators to identify functional and physical Interactions of larger numbers of proteins, the demand for detailed structural information will grow rapidly. The use of this Facility is therefore expected to grow significantly over the next five years. The services of the Facility will provide increasingly important information for understanding complex biological systems.
Almost all biological processes involve the interactions of proteins with other proteins or with DNA or small molecules, Structural information from molecular modeling helps to interpret existing experimental data on these interactions and to design new experiments to test biological hypotheses. Such experiments might include truncations of based on domain structures or mutations to disrupt specific interactions while leaving others intact.
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