BIOMOLECULAR INTERACTION AND GENE NETWORK SIMULATIONS

Carnegie-Mellon University, Pittsburgh PA

Investigators

Linked publications & trials

Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. a) Computer Simulations of Antimicrobial Peptides. Disease causing microbes are becoming resistant to common antibiotics, and are thus emerging as a serious threat to public health. Researchers are being forced to look for novel antibiotic formulations to combat this menace. Optimism in antimicrobial peptides (AMPs) as substitutes of conventional antibiotics has been triggered by knowledge of their quick and strong antimicrobial action, as well as the non-specific membrane-mediated mechanism of AMP-induced cell death. However, the design of novel AMPs with attenuated host cell toxicity has been impeded by a lack of molecular-scale fundamental knowledge of AMP-membrane interaction events. In our work, we use all-atom molecular dynamics simulations of AMPs in membrane mimics to decipher which sequence and structure components of AMPs are responsible for activity and toxicity b) Synthetic Bioengineering of Gene Regulatory Networks The ambitious idea of engineering cells that will function as miniature factories has given rise to new fields of research, systems and synthetic biology. We have developed multi-scale, stochastic simulation methods that can guide rational engineering of synthetic networks. Our method approximates fast and continuously occurring reactions as a continuous Markov process, but maintains slow or discontinuously occurring reactions in its original form, which is a jump Markov process. Because these two processes are highly coupled, their solution must proceed simultaneously.