Simulating the 3D conformations of intrinsically disordered transcriptional activation domains
Max Staller, Assistant Researcher
Center for Computational Biology
Applications for Fall 2024 are closed for this project.
It is now clear that roughly a third of the amino acids in human proteins are intrinsically disordered and do not fold into a single 3D structure. Some of these regions transiently fold when bound to partners, but many simply wiggle between many confirmations. These disordered regions cannot be visualized by most structural biology methods and are difficult to simulate with traditional molecular dynamics. Instead, we use all atom Monte Carlo simulations that been optimized for disordered sequences to simulate the different conformations these proteins can inhabit. We focus on the activation domains of transcription factors, regions that bind to coactivator protein complexes. Transcription factors contain activation domains and separate DNA binding domains. DNA binding domains are conserved, structured and can be predicted from amino acid sequence. Activation domains are intrinsically disordered and poorly conserved.
Role: Running all atom Monte Carlo simulations on the Savio cluster. Analyzing the trajectories of these simulations on the Savio cluster. Exploratory analysis of which features of the trajectories are correlated with activity.
Qualifications: Coursework in introductory biology and proficiency programming in python.
Experience with command line programming or working with the Savio cluster would be very helpful but is not required.
Chemistry 121 is highly recommended.
CS189 also highly recommended but not required.
In your essay, please describe any experience with 1) Savio 2) querying online databases 3) command line programming and 4) analysis in R or pandas. Experience with all 4 is not necessary, but each will be helpful.
Hours: 9-11 hrs
Biological & Health Sciences