PROJECT #16450 RESEARCH FOR CANCER
FOLDING PERFORMANCE PROFILE

PROJECT SUMMARY

This project seeks to understand G protein inhibition in the treatment of uveal melanoma and other G protein related diseases. G proteins are molecular switches regulate biological functions like sight, smell, and memory. This pivotal role makes G proteins essential players in physiology and pathophysiology. However, when G proteins mutate, they result in a variety of diseases from cancer to heart disease. For example, a single mutation in the Gq protein is known to cause uveal melanoma, a cancer in the iris of our eyes that remains largely untreatable short of removing the eye.

This project is simulating one of the G protein family isoforms, Gq, but in the ACTIVE form, bound to GTP. Other projects are simulating Gq, and other G proteins, in their "inactive" form, bound to GDP. The presence of the third phosphate in GTP is sufficient to convert G proteins into their active form. However, the ensemble of structures they adopt are not completely parsed out. By simulating the active form of Gq and comparing to other structures, we hope to provide a better understanding of G protein function. Furthermore, existing inhibitors of G proteins do not inhibit the GTP bound form, only the GDP-version, and understanding the "active ensemble" might provide a clearer picture as to why. 

PROJECT INFO

Manager(s): Sukrit Singh

Institution: Washington University in St. Louis

PROJECT WORK UNIT SUMMARY

Atoms: 66,619

Core: GRO_A7

Status: Public