Abstracts

This aritcle contains the abstracts of the various papers I have published or from presentations I have given.

Papers published

• Journal: Nucleic Acids Research, Vol. 32 No. 22 (14 December 2004)
• Title: "Distributions of Z-DNA and nuclear factor I in human chromosome 22: a model for coupled transcriptional regulation"
• Authors: P. Christoph Champ, Sandor Maurice, Jeffrey M. Vargason, Tracy Camp and P. Shing Ho

Abstract: An analysis of the human chromosome 22 genomic sequence shows that both Z-DNA forming regions (ZDRs) and promoter sites for nuclear factor-I (NFI) are correlated with the locations of known and predicted genes across the chromosome and accumulate around the transcriptional start sites of the known genes. Thus, the occurrence of Z-DNA across human genomic sequences mirrors that of a known eukaryotic transcription factor. In addition, 43 of the 383 fully annotated chromosomal genes have ZDRs within 2 nucleosomes upstream of strong NFIs. This suggests a distinct class of human genes that may potentially be transcriptionally regulated by a mechanism that couples Z-DNA with NFI activation, similar to the mechanism previously elucidated for the human colony stimulation factor-I promoter [Liu et al. (2001) Cell, 106, 309–318]. The results from this study will facilitate the design of experimental studies to test the generality of this mechanism for other genes in the cell.

Howard Hughes Medical Institute (HHMI)

• Session: 2001 HHMI Summer Undergraduate Research Program at OSU
• Title: "ZHuntIII: A Computer Approach To Mapping Z-DNA Within Human Chromosomes 21 and 22"
• Speaker: Christoph Champ

Abstract: In this project (ZHuntIII), we have developed several processes and programs in order to map the potential Z-DNA-forming sequences within the recently sequenced human chromosomes 21 and 22. The seven programs developed (collectively called ZHuntIII) employ rigorous thermodynamic search strategies, statistical mechanics, and pattern matching and comparison. ZHuntIII has been built upon past research, biochemical and biophysical principles, and computational techniques. The ZHuntIII search algorithm considers sequence type, length, and cooperativity to determine a "Z-Score" for a specified stretch of potential Z-DNA-forming nucleotides. The higher a Z-Score, the more likely that sequence is to adopt the Z conformation. Since every base pair within the chromosomes is assigned a Z-Score, we must choose only those Z-Scores that represent the highest likelihood in forming potential Z-DNA-forming sequences. In genomic sequences, these Z-Scores have been found to have values covering seven orders of magnitude. When plotting these values on a graph, the highest Z-Scores are easily visible as relatively few peaks raising several orders of magnitude among the majority of lower Z-Scores. We have chosen a threshold that is in the same order of magnitude as there are genes within human chromosomes 21 and 22. We expect this determination to compliment past research which has shown potential Z-DNA-forming sequences to occur upstream of the first expressed exon in a gene. That is, they are most commonly found near the 5' end of genes. We hope to show that this is also the case with most genes in much larger sequences, as those of human chromosomes 21 and 22.

• Session: 2001 HHMI Summer Undergraduate Research Program at OSU
• Title: "Mapping Z-DNA in Human Chromosome 22"
• Speaker: Christoph Champ

Abstract: missing

Conferences

• Session: Albany, New York
• Title: Map of Z-DNA in Human Chromosome 22 (poster #216)
• Presenter: P. Christoph Champ

Abstract: Although Z-DNA was discovered over 20 years ago, its function in a broad biological context remains largely undefined. We have subjected the sequence of human chromosome 22 to a rigorous thermodynamic search for this left-handed conformation using an extended version of the program Z-Hunt. The location of each potential Z-DNA forming region are compared relative to all the relevant markers for gene function, including known genes, pseudogenes, and open reading frames, and the relative positions within the genes and their exons and introns. The resulting map allows us to correlate this unusual structure with the functional elements of the human genome.

• Session: Sweden
• Title: FastContact
• Presenter: P. Christoph Champ

Abstract: Predicting protein-protein interactions involves sampling and scoring docked conformations. Barring some large structural rearrangement, rapidly sampling the space of docked conformations is now a real possibility, and the limiting step for the successful prediction of protein interactions is the scoring function used to reduce the space of conformations from billions to a few, and eventually one high affinity complex. An atomic level free energy scoring function that estimates both electrostatic and desolvation interactions in units of kcal/mol (plus van der Waals if appropriate) of protein-protein docked conformations is used to re-rank the blind predictions (860 in total) submitted for six targets to the community-wide Critical Assessment of PRediction of Interactions (CAPRI; http://capri.ebi.ac.uk). The score identifies native-like complexes as those with the lowest free energy for the models of 16 (out of 17) human predictors for five of the targets, while at the same time the modelers failed to do so in more than 50% of the cases. The correct scoring of high quality models developed by a wide variety of methods and force fields confirms that electrostatic and (de)solvation forces are the dominant protein interactions. Although for a given receptor/ligand either of these interactions might play a dominant role, only their complement offers a robust relative measure of the binding affinity for most systems. The CAPRI experiment has shown that modelers can predict excellent models of the co-crystals, and improvements on scoring functions should soon solve the docking problem for protein structures that do not change much upon binding. A scoring server and programs are available at http://structure.pitt.edu.