Structural Features of DNA Interaction with Amino Acid Conjugated Daunorubicin Derivatives

Abstract

The DNA sequence preferences of nucleosomes can be captured in a probabilistic model that ascribes a probability or, equivalently, an energy to any 147-bp sequence. This is generally done using a Markov chain model, where the total probability of a sequence is calculated from the probability distributions of subsequences of some length (usually dinucleotides) under the assumption that long-distance correlations are less important. These probability distributions must be trained on some subset of the entire sequence space, which has in the past been done experimentally, with certain statistical limitations and caveats. Using a novel simulation method, we are now able to produce large ensembles for training in silico, derived from an underlying energetic nucleosome model. This allows us for the first time to quantitatively examine how well such short-range probabilistic models approximate reality. In a next step, a probabilistic model trained on a quality sequence ensemble can then be used to predict energy landscapes for DNA sequences with negligible computational cost. This will allow us to test the idea that DNA may have evolved mechanical signals for nucleosome positioning, by simulating such evolution and comparing the patterns we find to patterns found in real genomes. 1995-Pos Board B139Continuously Scanning DNA with Nanopore MspA Nanopore sequencing is a promising next-generation technology that is being enabled by the biological nanopore MspA. In this sequencing technique, current is driven through the~1 nm constriction of MspA. Single stranded DNA molecules are first drawn into the pore by an applied voltage. Next, a polymerase or helicase moves the DNA by discrete steps as it interacts with the pore. As the DNA moves through the pore, different nucleobases modulate the pore's conductance to varying extents, allowing for extraction of sequence information from the current trace. In this experiment, we gain more complete information by using a variable applied voltage to stretch the DNA within the pore. Changing the voltage continuously repositions the DNA in the constriction. Coupling this voltage-induced movement with the enzyme-induced motion we reconstruct a profile characteristic of the DNA as it is pulled continuously through the constriction. This profile provides a tool for improving the de novo sequencing accuracy of the nanopore technique. of. Higher order chromatin structures and nuclear genome organization play a key role in regulating gene functions in addition to other epigenetic markers such as DNA and histone modifications, which have been extensively studied. Genetic variations in the human genome are known to lead to several human diseases but little is known yet about how the structural organization of the chromatin fibers affects gene regulation, cell differentiation, and disease pathways. Understanding the dynamics of native chromatin in living cells by imaging and tracing specific gene loci and nuclear transcripts would allow us to uncover the correlation between chromosome organizati...