Multiscale Models of Antibiotic Cellbots
The emergence of antibiotic resistant microorganisms poses an alarming threat to global health. Antimicrobial peptides (AMPs) are considered a possible effective alternative to conventional antibiotic therapies. These researchers engineer probiotic bacteria to produce and secrete antimicrobial peptides that target GI tract pathogens. They use mathematical models to guide our experimental designs. Work during the past years has resulted in the first quantitative narrative of how various classes of antimicrobial peptides work. The researchers continue studying AMPs that they use in probiotics.
Work in 2016 includes three projects:
- MD Simulations on the Class IIb Baceriocin PlnEF: The researchers have performed 500 ns of atomistic molecular dynamics simulations on two different configurations of the PlnEF dimer (one parallel and one antiparallel positioning of the two peptides with respect to each other), inside a model lipid bilayer that resembles the membrane of Gram-positive bacteria. They have started simulating mutants of PlnEF in order to enlighten the importance of the presence of specific aminoacid residues and motifs. There are six important mutations that they are studying (twelve new systems, since they simulate two conformations, suggested by NMR experiments), stemmed by the group's wild-type simulations as well as experimental data.
- MD Simulations on Protegrin-Type AMPs: The researchers will perform similar analysis on protegrin-type AMPs as they do on the PlnEF system. Specifically, they are simulating two different structure pores (PG-1 and PC-64) for 500 ns. Previous results showed this timescale is necessary for pore stabilization and ion transfer.
- Stochastic Simulations of Gene Network: A stochastic simulation of a gene network is composed of an ensemble of independent trajectory trials. Ensembles of those trials produce probability distributions of the possible dynamics. Because each trial is independent (typical trial numbers vary from 10,000 up to 1,000,000 trials), they may be executed on different processors completely asynchronously. The combination of a highly parallelizable problem, portable source code, and platform independent I/O creates a good fit between this research and MSI's architecture. During 2016, these researchers hope to continue exploring systems such as the prgX/prgQ operon or the ProteOn operon (with two different configurations). Particularly, they focus on engineering novel behavior and optimizing the natural form to better suit the needs of synthetic biology. They are designing and simulating a large number of systems with variations in kinetic constants and gene network topology in order to achieve the desired behaviors. Systems that show promising results will then be constructed and tested in vivo in the laboratory.
A Research Spotlight about this research appeared on the MSI website in January 2014.
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