Hierarchical molecular dynamics sampling for assessing pathways and free energies of RNA catalysis, ligand binding, and conformal change

Thomas Cheatham, University of Utah

Usage Details

Thomas Cheatham, Tai-Sung Lee, Andre Merzky, Adrian Roitberg, John Chodera, Daniel Roe, Romelia Salomon, Ross Walker, Christina Bergonzo, Hai Nguyen, Terry McGee, Billy Miller III, Jason Swails, Niel Henriksen, Andreas Goetz, Kalyana Chadalavada, George Giambasu, Johan Galindo-Cruz, Ben Madej, James Maier, Thakshila Dissanayake Rallage, Pawel Janowski, Maria Panteva, Mark Santcroos, Kevin Hauser, Robin Betz, Rodrigo Galindo, Daniel Parton, Brian Radak, Shuai Liang, Chad Hopkins, Sean Cornillie, James Robertson, Letif Mones, Davide Sabbadin, Natali Di Russo, Patrick Grinaway, Siddhartha Abhinav, Pancham Lal Gupta, Kenneth Lam, Jinfeng Liu, Jordi Juarez-Jimenez, He Huang, Koushik Kasavajhala, Justin Smith, Ankita Sarkar, Dylan MacPhee, Antons Treikalis, Travis Hughes

The research team is attempting to decipher the full landscape of RNA structure and function. Understanding RNA is challenging because not only does it require modeling the flexibility and subtle balance between charge, stacking and other molecular interactions, but the structure of RNA is highly sensitive to its surroundings, and RNA can adopt multiple functionally relevant conformations. The main goals of this project are to hierarchically and tightly couple a series of optimized molecular dynamics engines to fully map out the conformational, energetic and chemical landscape of RNA. Molecular dynamics engines that are optimized at the supernode level will be coupled and will exchange information to better sample and interpret the free energy landscape.

"Essentially we are able to push enhanced sampling methodologies for molecular dynamics simulation, specifically replica-exchange, to complete convergence for conformational ensembles (which hasn't really been investigated previously) and perform work that normally would take 6 months to years in weeks. This is critically important for validating and assessing the force fields for nucleic acids," explains Cheatham.

http://home.chpc.utah.edu/~cheatham/