Z-Hunt

ZHUNT (aka Z-Hunt or ZHunt) is an algorithm for predicting the propensity of DNA to flip from the B-form to the Z-form. The original algorithm was written by Dr. P. Shing Ho in 1986 and was later developed by Tracy Camp, P. Christoph Champ, Sandor Maurice, and Jeffrey M. Vargason for genome-wide mapping of Z-DNA (with P. Shing Ho as the principal investigator). ZHUNT is available for use Online at ZHunt Online.

Introduction

Description

ZHUNT was constructed as a program to predict the formation of Z-DNA for any sequence of n dinucleotides. A branching algorithm is used to find the minimum total propagation energy for the sequence to assign the ΔG° values to calculate the propagation term (S) for each dinucleotide in the simple set of nested DO LOOPS for the product and summation terms of Q and <ΔTw> as the program walks through a sequence. The complete output from the includes the "best" stretch of Z-DNA dinucleotides in the sequence, the anti-syn assignments for the dinucleotides in this stretch, the <ΔTw> and the ΔLk_m for the stretch—the lower the ΔLk_m, the higher the potential that the sequence will form Z-DNA.

In order for the ΔLk_m values to be useful as a predictive tool, they are converted to propensities for forming Z-DNA relative to random sequences. Thus, the ΔLk_m value is compared to those for a set of randomly generated sequences to calculate a propensity (originally called a Z-score, but now referred to a P_Z), which reflects the propensity for the sequence to form Z-DNA. P_Z for a particular sequence is defined as the number of random sequences that one must search in order to find one that has a similar or higher propensity to form Z-DNA, and has units of base pairs (bp).

Terms

ΔLk_m 

linking number

<ΔTw> 

change in helical twist

ΔWr 

change in writhe = ΔWr = ΔLk_m – <ΔTw>

ΔG° 

overall energy associated with the transition from B-DNA to Z-DNA; ΔG° = K(ΔLk_m – ΔTw_m)²

K 

K = 1100RT/N, for N number of base pairs in the DNA plasmid (see: for description)

Q 

partition function

for propagation of Z-DNA through n number of dinucleotides, and 0.179 is the ΔTw for each dinucleotide and 0.4 is the ΔTw of the two B–Z junctions.

<ΔTw> 

change in overall helical twist

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Z-score

Note: The following table is a list of test sequences with their corresponding conformational assignments and Z-scores (now called "P_Z" scores). This "Z-score" should not be confused with the statistical "Standard score". Here, it describes the propensity of a given sequence to adopt the left-handed form of DNA; it is simply a probability score.

Sequence/conf. assignments | Z-score ----------------------------|------------ CGCGCGCGCGCGCGCGCGCGCGCG | 2 x 10e+11 ASASASASASASASASASASASAS | | CGCGCGCGCGCG | 4 x 10e+07 ASASASASASAS | | CACACACACACACACACACACACA | 2 x 10e+05 ASASASASASASASASASASASAS | | CACACACACACA | 2 x 10e+04 ASASASASASAS | | CGCGCGCGCGCG GCGCGCGCGCGC | 2 x 10e+08 ASASASASASAS SASASASASASA | | CGCGCG GCGCGC CGCGCG GCGCGC | 7 x 10e+04 ASASAS SASASA ASASAS SASASA | | * * * * * * | CCCGCCCGCCCGCCCGCCCGCCCG | 8 x 10e+04 ASASASASASASASASASASASAS | | * * * * * * | CAGGCAGGCAGGCAGGCAGGCAGG | 1 x 10e+03 ASASASASASASASASASASASAS | | * * * * * * * * * * * * | CCCCCCCCCCCCCCCCCCCCCCCC | 52 ASASASASASASASASASASASAS | | ATATATATATATATATATATATAT | 38 SASASASASASASASASASASASA | | AAAAAAAAAAAAAAAAAAAAAAAA | 3 x 10e-07 ASASASASASASASASASASASAS |

Various test sequences are shown with their corresponding Z-score as assigned by Z-hunt [version 1]. Z-scores are defined as the number of random base pairs that must be scanned, on average, to find a sequence with equal or better Z-forming capacity relative to the sequence in question. The conformation selected by Z-hunt for each nucleotide (A for anti and S for syn) are indicated below each sequence. Bases which deviate from perfect purine-pyrimidine alternation are designated by dots above that nucleotide. Discontinuities in the conformational phases produced by Z-Z junctions are represented by gaps separating the sequence.

Keywords and abbreviations

• Keywords: Z-DNA; Nuclear factor I; Transcription regulation; Thermogenomics
• Abbreviations: ZDR, potential Z-DNA regions; NFI, nuclear factor I; CSF, colony stimulating factor

See also

• Z-DNA
• wikipedia:DNA supercoil
• wikipedia:Gibbs free energy
• wikipedia:Topoisomerase
• wikipedia:Linking number
• wikipedia:Möbius strip

References

Further reading

• Ho PS (2008). "Thermogenomics: Thermodynamic-based approaches to genomic analyses of DNA structure". Methods, [Epub ahead of print]. PMID: 18848994. DOI:10.1016/j.ymeth.2008.09.007
• Ho PS (1994). The non-B-DNA structure of d(CA/TG)n does not differ from that of Z-DNA. Proc Natl Acad Sci USA, 91(20):9549-9553.
• Schroth GP, Chou PJ, Ho PS (1992). Mapping Z-DNA in the human genome. Computer-aided mapping reveals a nonrandom distribution of potential Z-DNA-forming sequences in human genes. J Biol Chem, 267(17):11846-55.

External links

• ZHunt Online Server (website currently offline) — front end by Sandor Maurice; back end by Sandor Maurice and P. Christoph Champ.
• non-B DB — a database of predicted non-B DNA-forming motifs and its associated tools.
• make-na server — create custom DNA structures (in PDB format)