Understanding DNA surface interactions for systems design and engineering
EMSL Project ID
47761
Abstract
DNA replication, DNA modification, and single organism engineering are being used in many fields of relevance to the DOE mission. Extensive knowledge of the fundamental reactions involved in these processes will continue to aid the design and engineering processes involved with biofuels and geobacter remediation strategies. This project will examine two fundamental and critical aspects of DNA chemistry and physics; DNA-protein interactions and the ability of proteins to quickly locate their DNA target, and DNA folding in a small volume. First, proteins and DNA interact in many biological functions. How do these two molecules locate the specific site needed for the correct protein-DNA complex formation? Secondly, the mechanism, used in nature, to pack a highly-negatively charge molecule, such as DNA, into a confined, biologically relevant space. When a protein binds to a DNA molecule, necessary for function, the interaction can be a specific or a non-specific interaction. The mechanisms governing protein-DNA recognition and the transition of proteins from their unfolded state to their native state are unanswered. Refolding often occurs in DNA binding. Multiscale simulations including molecular dynamics simulations coupled with Brownian dynamics will be performed to understand the encounter and complex formation. Details of the interfacial properties of the sequence-dependent protein-DNA landscape will also be calculated. Additionally, recent experimental data from one of our collaborators has indicated that specific amino acid residues, in particular lysine and arginine, appear to play a more important role in the protein-DNA dynamic location/recognition process. Using our 2 sets of DNA/protein simulations, this rarely investigated amino acid effect on dynamics will also be analyzed.
Understanding the biophysical basis of the biological process which transfers a viral genome to infect a cell is important to the cellular machinery and many bacteria engineering related fields. Predicting the thermodynamic pressures including the osmotic pressure necessary to confine certain sequences of DNA in a specific volume, like a phage capsids with over 250-fold compaction, is a problem with implications in bionanotechnology, and phage delivery of genetic messages. We will resolve questions of the thermodynamic mechanism of DNA ejection by phages by designing coarse-grained models in conjunction with using detailed all-atom calculations and experimental thermodynamic and structural data.
Project Details
Project type
Exploratory Research
Start Date
2013-02-13
End Date
2013-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Chen C ,Pettitt B M 2016. "DNA Shape versus Sequence Variations in the Protein Binding Process" Biophysical Journal 110(3):534–544. 10.1016/j.bpj.2015.11.3527