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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
Project #
Application #
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Research Institute of Fox Chase Cancer Center
United States
Zip Code
Austin, Steven R; Wong, Yu-Ning; Uzzo, Robert G et al. (2015) Why Summary Comorbidity Measures Such As the Charlson Comorbidity Index and Elixhauser Score Work. Med Care 53:e65-72
Bassi, Daniel E; Cenna, Jonathan; Zhang, Jirong et al. (2015) Enhanced aggressiveness of benzopyrene-induced squamous carcinomas in transgenic mice overexpressing the proprotein convertase PACE4 (PCSK6). Mol Carcinog 54:1122-31
Sherman, Kerry A; Miller, Suzanne M; Roussi, Pagona et al. (2015) Factors predicting adherence to risk management behaviors of women at increased risk for developing lymphedema. Support Care Cancer 23:61-9
Eytan, Esther; Wang, Kexi; Miniowitz-Shemtov, Shirly et al. (2014) Disassembly of mitotic checkpoint complexes by the joint action of the AAA-ATPase TRIP13 and p31(comet). Proc Natl Acad Sci U S A 111:12019-24
Johnson, Matthew E; Handorf, Elizabeth A; Martin, Jeffrey M et al. (2014) Postmastectomy radiation therapy for T3N0: a SEER analysis. Cancer 120:3569-74
Gabitova, Linara; Gorin, Andrey; Astsaturov, Igor (2014) Molecular pathways: sterols and receptor signaling in cancer. Clin Cancer Res 20:28-34
Silverman, Diana; Ruth, Karen; Sigurdson, Elin R et al. (2014) Skin involvement and breast cancer: are T4b lesions of all sizes created equal? J Am Coll Surg 219:534-44
Gupta, Sapna; Melnyk, Stepan B; Kruger, Warren D (2014) Cystathionine *-synthase-deficient mice thrive on a low-methionine diet. FASEB J 28:781-90
Simhan, Jay; Smaldone, Marc C; Egleston, Brian L et al. (2014) Nephron-sparing management vs radical nephroureterectomy for low- or moderate-grade, low-stage upper tract urothelial carcinoma. BJU Int 114:216-20
Gowrishankar, Banumathy; Ibragimova, Ilsiya; Zhou, Yan et al. (2014) MicroRNA expression signatures of stage, grade, and progression in clear cell RCC. Cancer Biol Ther 15:329-41

Showing the most recent 10 out of 475 publications