Assistant ProfessorOffice: C117Phone: 970-491-3572Website: http://sites.chem.colostate.edu/mccullaghlab/index.htmlEducation: Ph.D., Northwestern UniversityEmail: Martin.McCullagh@colostate.edu
The chemistry of protein-DNA interactions will be investigated using a systematic multiscale computational and theoretical approach. Mechanistic insight into DNA repair enzymes will be sought with the coupling of all-atom molecular dynamics (MD) and quantum mechanics (QM). The self-assembly of novel biomaterials as well as the assembly of chromatin in the cell nucleus will be investigated using coarse-grained (CG) models designed with the necessary physics to treat such systems. The insights gained from these projects will have impact in the fundamental understanding of self-assembly as well as the system specific chemistry. The methods developed for CG self-assembly will push the frontiers of multiscale simulation. DNA Repair Enzymes Repair of DNA damage from both endogenous and exogenous agents is a natural cellular defense mechanism but also limits the effectiveness of DNA targeting chemotherapy drugs. One of the major DNA repair pathways is base excision repair (BER) in which mutated bases are excised followed by the removal of the resulting abasic site. Molecular dynamics (MD) coupled with quantum mechanics-molecular mechanics (QM/MM) techniques will be employed to study the mechanism of BER for a particular glycolysase. Self-assembled Biomaterials Delivering genetic material to the cell is a promising anticancer therapy in which DNA encoding a functional gene is delivered to a cell that is producing the mutated form of the same gene. Delivery of DNA requires protection of the genetic material in the extracellular region as well as release of the delivery load in the cytoplasm or nucleus. A promising material for this function is self-assembling peptides. A recent experimental study by Ruff et al has synthesized and assembled such a material. Coarse-grain simulations of these systems can help provide insight into the self-assembly process and structure and eventually lead to better design criteria for these materials. Chromatin Packing All protein-DNA interactions in eukaryotic cells happen with DNA highly condensed in the nucleus. There, DNA wraps around proteins to form nucleosomes than, in turn, assemble into chromatin. Starting with the atomic scale, a hierarchy of models will be built and simulated in order to gain a better understanding of the underlying forces leading to chromatin assembly.