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The Relationship Between DNA's Physical Properties and the DNA Molecule's Harmonic Signature, and Related Motion in Water--A Computational Investigation
Title
The Relationship Between DNA's Physical Properties and the DNA Molecule's Harmonic Signature, and Related Motion in Water--A Computational Investigation.
Creator
Boyer, Victor, Proctor, Michael, Thompson, William, Karwowski, Waldemar, Calloway, Richard, University of Central Florida
Abstract / Description
This research investigates through computational methods whether the physical properties of DNA contribute to its harmonic signature, the uniqueness of that signature if present, and motion of the DNA molecule in water. When DNA is solvated in water at normal 'room temperature', it experiences a natural vibration due to the Brownian motion of the particles in the water colliding with the DNA. The null hypothesis is that there is no evidence to suggest a relationship between DNA's motion and...
Show moreThis research investigates through computational methods whether the physical properties of DNA contribute to its harmonic signature, the uniqueness of that signature if present, and motion of the DNA molecule in water. When DNA is solvated in water at normal 'room temperature', it experiences a natural vibration due to the Brownian motion of the particles in the water colliding with the DNA. The null hypothesis is that there is no evidence to suggest a relationship between DNA's motion and strand length, while the alternative hypothesis is that there is evidence to suggest a relationship between DNA's vibrational motion and strand length. In a similar vein to the first hypothesis, a second hypothesis posits that DNA's vibrational motion may be dependent on strand content. The nature of this relationship, whether linear, exponential, logarithmic or non-continuous is not hypothesized by this research but will be discovered by testing if there is evidence to suggest a relationship between DNA's motion and strand length. The research also aims to discover whether the motion of DNA, when it varies by strand length and/or content, is sufficiently unique to allow that DNA to be identified in the absence of foreknowledge of the type of DNA that is present in a manner similar to a signature. If there is evidence to suggest that there is a uniqueness in DNA's vibrational motion under varying DNA strand content or length, then additional experimentation will be needed to determine whether these variances are unique across small changes as well as large changes, or large changes only. Finally, the question of whether it might be possible to identify a strand of unique DNA by base pair configuration solely from its vibrational signature, or if not, whether it might be possible to identify changes existing inside of a known DNA strand (such as a corruption, transposition or mutational error) is explored. Given the computational approach to this research, the NAMD simulation package (released by the Theoretical and Computational Biophysics Group at the University of Illinois at Urbana-Champaign) with the CHARMM force field would be the most appropriate set of tools for this investigation (Phillips et al., 2005), and will therefore be the toolset used in this research. For visualization and manipulation of model data, the VMD (Visual Molecular Dynamics) package will be employed. Further, these tools may be optimized and/or be aware of nucleic acid structures, and are free. These tools appear to be sufficient for this task, with validated fidelity of the simulation to provide vibrational and pressure profile data that could be analyzed; sufficient capabilities to do what is being asked of it; speed, so that runs can be done in a reasonable period of time (weeks versus months); and parallelizability, so that the tool could be run over a clustered network of computers dedicated to the task to increase the speed and capacity of the simulations. The computer cluster enabled analysis of 30,000 to 40,000 atom systems spending more than 410,000 CPU computational hours of hundreds of nano second duration, experimental runs each sampled 500,000 times with two-femtosecond (")frames.(")Using Fourier transforms of run pressure readings into frequencies, the simulation investigation could not reject the null hypotheses that the frequencies observed in the system runs are independent on the DNA strand length or content being studied. To be clear, frequency variations were present in the in silicon replications of the DNA in ionized solutions, but we were unable to conclude that those variations were not due to other system factors. There were several tests employed to determine alternative factors that caused these variations. Chief among the factors is the possibility that the water box itself is the source of a large amount of vibrational noise that makes it difficult or impossible with the tools that we had at our disposal to isolate any signals emitted by the DNA strands. Assuming the water-box itself was a source of large amounts of vibrational noise, an emergent hypothesis was generated and additional post-hoc testing was undertaken to attempt to isolate and then filter the water box noise from the rest of the system frequencies. With conclusive results we found that the water box is responsible for the majority of the signals being recorded, resulting in very low signal amplitudes from the DNA molecules themselves. Using these low signal amplitudes being emitted by the DNA, we could not be conclusively uniquely associate either DNA length or content with the remaining observed frequencies. A brief look at a future possible isolation technique, wavelet analysis, was conducted. Finally, because these results are dependent on the tools at our disposal and hence by no means conclusive, suggestions for future research to expand on and further test these hypothesis are made in the final chapter.
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Date Issued
2015
Identifier
CFE0005930, ucf:50835
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0005930
Homologous Pairing Through DNA Driven Harmonics - A Simulation Investigation
Title
Homologous Pairing Through DNA Driven Harmonics - A Simulation Investigation.
Creator
Calloway, Richard, Proctor, Michael, Kincaid, John, Jaganathan, Balasubramanian, Gerber, Matthew, Chai, Xinqing, University of Central Florida
Abstract / Description
The objective of this research is to determine if a better understanding of the (")molecule of life("), deoxyribonucleic acid or DNA can be obtained through Molecular Dynamics (MD) modeling and simulation (M(&)S) using contemporary MD M(&)S. It is difficult to overstate the significance of the DNA molecule. The now-completed Human Genome Project stands out as the most significant testimony yet to the importance of understanding DNA. The Human Genome Project (HGP) enumerated many areas of...
Show moreThe objective of this research is to determine if a better understanding of the (")molecule of life("), deoxyribonucleic acid or DNA can be obtained through Molecular Dynamics (MD) modeling and simulation (M(&)S) using contemporary MD M(&)S. It is difficult to overstate the significance of the DNA molecule. The now-completed Human Genome Project stands out as the most significant testimony yet to the importance of understanding DNA. The Human Genome Project (HGP) enumerated many areas of application of genomic research including molecular medicine, energy sources, environmental applications, agriculture and livestock breeding to name just a few. (Science, 2008) In addition to the fact that DNA contains the informational blueprints for all life, it also exhibits other remarkable characteristics most of which are either poorly understood or remain complete mysteries. One of those completely mysterious characteristics is the ability of DNA molecules to spontaneously segregate with other DNA molecules of similar sequence. This ability has been observed for years in living organisms and is known as (")homologous pairing.(") It is completely reproducible in a laboratory and defies explanation. What is the underlying mechanism that facilitates long-range attraction between 2 double-helix DNA molecules containing similar nucleotide sequences? The fact that we cannot answer this question indicates we are missing a fundamental piece of information concerning the DNA bio-molecule. The research proposed herein investigated using the Nano-scale Molecular Dynamics NAMD (Phillips et al., 2005) simulator the following hypotheses:H(Simulate Observed Closure NULL) : = Current MD force field models when used to model DNA molecule segments, contain sufficient variable terms and parameters to describe and reproduce directed segregating movement (closure of the segments) as previously observed by the Imperial College team between two Phi X 174 DNA molecules. H(Resonance NULL) : = Current MD force field models when used to model DNA molecule segments in a condensed phased solvent contain sufficient variable terms and parameters to reproduce theorized molecular resonation in the form of frequency content found in water between the segments. H(Harmonized Resonance NULL) : = Current MD force field models of DNA molecule segments in a condensed phase solvent produce theorized molecular resonation in the form of frequency content above and beyond the expected normal frequency levels found in water between the segments. H(Sequence Relationship NULL): = The specific frequencies and amplitudes of the harmonized resonance postulated in H(Harmonized Resonance NULL) are a direct function of DNA nucleotide sequence. H(Resonance Causes Closure NULL) : = Interacting harmonized resonation produces an aggregate force between the 2 macro-molecule segments resulting in simulation of the same directed motion and segment closure as observed by the Imperial College team between two Phi X 174 DNA molecules. After nearly six months of molecular dynamic simulation for H(Simulate Observed Closure NULL) and H(Resonance Causes Closure NULL) no evidence of closure between two similar sequenced DNA segments was found. There exist several contributing factors that potentially affected this result that are described in detail in the Results section. Simulations investigating H( Resonance NULL), H(Harmonized Resonance NULL) and the emergent hypothesis H(Sequence Relationship NULL) on the other hand, revealed a rich selection of periodic pressure variation occurring in the solvent between simulated DNA molecules. About 20% of the power in Fourier coefficients returned by Fast Fourier Transforms performed on the pressure data was characterized as statistically significant and was located in less than 2% of the coefficients by count. This unexpected result occurred consistently in 5 different system configurations with considerable system-to-system variation in both frequency and magnitude. After careful analysis given the extent of our experiments the data was found to be in support of H( Resonance NULL), and H(Harmonized Resonance NULL) . Regarding the emergent hypothesis H(Sequence Relationship NULL), further analysis was done on the aggregate data set looking for correlation between nucleotide sequence and frequency/magnitude. Some of the results may be related to sequence but were insufficient to prove it. Overall the conflicting results were inconclusive so the hypothesis was neither accepted nor rejected. Of particular interest to future researchers it was noted that the computational simulations performed herein were NOT able to reproduce what we know actually happens in a laboratory environment. DNA segregation known to occur in-vitro during the Imperial College investigation did not occur in our simulation. Until this discrepancy is resolved MM simulation should not as yet be considered a suitable tool for further investigation of Homologous Chromosome Pairing. In Chapter 5 specific follow on research is described in priority of need addressing several new questions.
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Date Issued
2011
Identifier
CFE0004472, ucf:49302
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0004472