R35GM141881

Prediction of the Structures of Protein Complexes - Prediction of the Structures of Protein Complexes

Jeffrey J. Gray, NIGMS R35 (MIRA) Project Summary

Protein interactions are involved in nearly all biological processes in human health and diseases, and protein complex structures can reveal biological mechanisms and suggest intervention strategies. Computational modeling provides an alternative route to elucidate structures. Modeling also tests our understanding of molecular biophysics and allows us to engineer molecules based on their structures.

My lab is a pioneer in developing computational methods to predict and design protein-protein interfaces and in applying those methods broadly, from immunology and cancer to infectious disease and tissue engineering. Our central focus is on protein-protein docking, that is, predicting the structure of a complex from the components (individual polypeptides or domains). A longstanding challenge in docking is correctly capturing protein conformational change, and we lead development of innovative search strategies and rapid scoring schemes to close this gap.

Another focus area is the modeling and design of antibodies, directly supporting drug and diagnostic agent development and optimization. We predict high-resolution antibody structures from sequence, dock those models to antigens, and design antibodies to target specific antigens.

Several protein modifications are important to consider when modeling interfaces. The emergence of powerful experimental methods for characterizing glycans has prompted us to expand our tools to model carbohydrates including docking methods and focused studies on glycotransferases.

All our methods are embedded in the Rosetta software platform, which is used by tens of thousands of academic and industry scientists worldwide. The utility of our work is evidenced by the high demand for our prediction and design web server, scripting platform, and teaching materials.

By leading the technical and scientific testing operations for the Rosetta Commons, my lab powers the synergies to combine Rosetta's powerful biomolecular prediction and design methods across this international collaboration.

The Johns Hopkins University

THE NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES (NIGMS) SUPPORTS BASIC RESEARCH THAT INCREASES OUR UNDERSTANDING OF BIOLOGICAL PROCESSES AND LAYS THE FOUNDATION FOR ADVANCES IN DISEASE DIAGNOSIS, TREATMENT, AND PREVENTION. NIGMS ALSO SUPPORTS RESEARCH IN SPECIFIC CLINICAL AREAS THAT AFFECT MULTIPLE ORGAN SYSTEMS: ANESTHESIOLOGY AND PERI-OPERATIVE PAIN, CLINICAL PHARMACOLOGY ?COMMON TO MULTIPLE DRUGS AND TREATMENTS, AND INJURY, CRITICAL ILLNESS, SEPSIS, AND WOUND HEALING.? NIGMS-FUNDED SCIENTISTS INVESTIGATE HOW LIVING SYSTEMS WORK AT A RANGE OF LEVELSFROM MOLECULES AND CELLS TO TISSUES AND ORGANSIN RESEARCH ORGANISMS, HUMANS, AND POPULATIONS. ADDITIONALLY, TO ENSURE THE VITALITY AND CONTINUED PRODUCTIVITY OF THE RESEARCH ENTERPRISE, NIGMS PROVIDES LEADERSHIP IN SUPPORTING THE TRAINING OF THE NEXT GENERATION OF SCIENTISTS, ENHANCING THE DIVERSITY OF THE SCIENTIFIC WORKFORCE, AND DEVELOPING RESEARCH CAPACITY THROUGHOUT THE COUNTRY.

93.859 - Biomedical Research and Research Training

National Institute of General Medical Sciences (NIGMS) [HHS - NIH]

Baltimore, Maryland 212182608 United States

Single Zip Code

Maximizing Investigators' Research Award (R35 - Clinical Trial Optional) (PAR-19-367)

Amendment Since initial award the total obligations have increased 439% from $720,181 to $3,883,900.