Styron Pereira
Pronouns:
Research Mentor(s): Furyal Ahmed
Research Mentor School/College/Department: Biophysics / LSA
Program:
Authors: Styron Pereira, Furyal Ahmed, Charles L. Brooks III
Session: Session 4: 1:40 pm – 2:30 pm
Poster: 32
Abstract
Src-kinase is a proto-oncogene that is responsible for regulation processes that occur in many protein pathways in the body. However, it can become constitutively active by adopting one of two conformational states (the open state) in cancerous cells. Therefore, understanding the mechanisms that affect conformational changes in Src-kinase could provide a basis to help control relevant biological processes during disease treatments. Previous research regarding Src-family kinases used Go-models to study conformational change in the protein’s kinase domain1. Go-like models are coarse-grained molecular mechanics models that represent the protein architecture by the backbone Ca atoms with interactions only between atoms corresponding to residue pairs that form favorable interactions in the native state2. Using a similar method, Go-like models were used in molecular dynamics simulations to study the native states and changes over time of the entire Src-kinase protein to explore excursions between the open state (given by PDB ID: 1Y57) and the closed state (given by PDB ID: 2SRC) conformations in the wildtype protein. By varying the temperature and length of the simulations, we found ideal simulation conditions that showed the maximum possible reasonable activity we would expect. By doing 5 replicants, and by starting from both open and closed conformations, we recorded residue-residue pairwise distances and did dimensional analyses. By using this data, we can analyze and compare the changes in conformation that occur due to altered residue interactions of the protein, which can potentially create an energetically favorable closing conformational change. This information can then be used to develop protein drugs that function like the mutants and can close the Src-kinase conformation in cancerous cells in the body. Our current results provide a foundation for this analysis and show important residue-residue interactions that define the type and range of the protein’s conformation.
