Semester of Graduation
Spring 2026
Degree Type
Dissertation/Thesis
Degree Name
Masters in Information Technology
Department
College of Computing and Software Engineering
Committee Chair/First Advisor
Yixin Xie
Second Advisor
Seyedamin Pouriyeh
Third Advisor
Bobin Deng
Abstract
GPR56 (ADGRG1) is an adhesion G protein-coupled receptor implicated in brain development, glioblastoma, and myelination. The cryo-EM structure 7SF8 captures GPR56 in its active state, bound to a tethered agonist and a heterotrimeric G protein. Cryo-EM gives a static snapshot. Molecular dynamics (MD) simulation is needed to test which contacts persist under thermal motion. This thesis ran two independent 200 ns MD simulations of the 7SF8 complex (14,977 atoms, four chains) using OpenMM 8.2. The two runs used AMBER ff19SB with OPC water and AMBER ff99SB with TIP3P water. Cross-force field consistency was used to screen out parameter specific artifacts. Contact was reported only when its occupancy reached at least 50% in both runs. Both simulations converged within 50 ns. Salt bridge analysis identified four GPR56 intrachain contacts at 100% occupancy in both runs: ASP14-HIS17, ASP152-ARG88, GLU84-ARG88, and GLU108-HIS58. Mean distances were 2.71 - 2.84 Å. Interchain analysis identified thirteen cross-force field consistent salt bridges. The primary biological finding is three GPR56-Gα13 coupling contacts at ≥99.9% occupancy in both runs: B:ASP217-A:ARG210, A:GLU118-B:ARG32, and B:ASP222-A:ARG51. The remaining ten contacts validate Gαβγ heterotrimer integrity. These results generate testable site directed mutagenesis hypotheses. Priority targets are A:ARG210, A:GLU118, and A:ARG51 on GPR56, and their Gα13 partners.