Electrostatic interactions are signiﬁcant for biomolecules given the prevalence of electric charges in all major families of biomolecules (e.g., DNA/RNA, proteins, and lipids). Precise and predictable knowledge of biomolecular electrostatics has thus been a longstanding goal in biophysics. While the physical laws of electrostatics are well-established, biomolecular electrostatics presents formidable challenges due to the sheer size of the multi-component system in a salty aqueous environment. As a result, our understanding of biomolecular electrostatics is far from complete, despite extensive eﬀorts in the past decades. My dissertation research focuses on the model system of nucleic acids helices and aims to elucidate the role of molecular structure, largely ignored up to now, in electrostatic interactions.
Speciﬁcally, we probe how structures of nucleic acids and peptides aﬀect the electrostatic interactions between nucleic acid helices by osmotic stress method and x-ray diﬀraction (XRD). Diﬀerent DNA/RNA sequences and surface modiﬁcations are used to produce the various helical structures of nucleic acids, osmotic stress is used to vary the forces between nucleic acid helices (DNA-DNA or RNA-RNA), and XRD is used to measure the inter-helical spacing. Consequently, our measurement yields the quantitative relationship between DNA-DNA force and DNA-DNA spacing.
Our ﬁrst-of-its-kind measurement discovers and quantiﬁes structure-dependent behaviors in force-spacing relations of DNA-DNA and RNA-RNA interactions that appear to be strongly correlated with the incurred structural changes. Furthermore, DNA-DNA forces modulated by the peptides, selected from histone tails with different charges and sequences are measured. The force curves are found to depend on both the total charge and sequence of the peptides, revealing speciﬁc (peptide-sequence modulated) and non-speciﬁc (charge modulated) interactions with DNA. More broadly, our observations bear biological implications concerning chromatin conformation and epigenetic regulations, and possible future directions include studies of additional biological nucleic acids and peptides sequences, molecular dynamics simulations (MD), and bioinformatic analyses.
|Commitee:||Peng, Weiqun, Reeves, Mark, Afanasev, Andrei, Liu, Xitong|
|School:||The George Washington University|
|School Location:||United States -- District of Columbia|
|Source:||DAI-B 81/7(E), Dissertation Abstracts International|
|Keywords:||Structure-modulated electrostatic interactions, Nucleic acid helices|
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