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Fuhai Li Xiaobo Zhou Wanting Huang Chung-Che Chang Stephen TC Wong 《BMC bioinformatics》2010,11(1):200
Background
DNA copy number aberration (CNA) is very important in the pathogenesis of tumors and other diseases. For example, CNAs may result in suppression of anti-oncogenes and activation of oncogenes, which would cause certain types of cancers. High density single nucleotide polymorphism (SNP) array data is widely used for the CNA detection. However, it is nontrivial to detect the CNA automatically because the signals obtained from high density SNP arrays often have low signal-to-noise ratio (SNR), which might be caused by whole genome amplification, mixtures of normal and tumor cells, experimental noise or other technical limitations. With the reduction in SNR, many false CNA regions are often detected and the true CNA regions are missed. Thus, more sophisticated statistical models are needed to make the CNAs detection, using the low SNR signals, more robust and reliable. 相似文献3.
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Background
Owing to rapid expansion of protein structure databases in recent years, methods of structure comparison are becoming increasingly effective and important in revealing novel information on functional properties of proteins and their roles in the grand scheme of evolutionary biology. Currently, the structural similarity between two proteins is measured by the root-mean-square-deviation (RMSD) in their best-superimposed atomic coordinates. RMSD is the golden rule of measuring structural similarity when the structures are nearly identical; it, however, fails to detect the higher order topological similarities in proteins evolved into different shapes. We propose new algorithms for extracting geometrical invariants of proteins that can be effectively used to identify homologous protein structures or topologies in order to quantify both close and remote structural similarities. 相似文献5.
A solid-phase synthesis for a DNA analogue with a mixed guanidinium and urea backbone is reported. This material is nearly identical in structure to deoxynucleic guanidine (DNG) but the neutral urea internucleoside linkages can be used to attenuate the overall positive charge on the oligomer. The opposite charge attraction between urea containing DNG oligomers (DNGUs) and complimentary DNA can be controlled so that the affinity of DNG for DNA does not overwhelm the base-pairing discrimination necessary for specific binding. Octameric DNGU containing between 1 and 3 urea substitutions covered the range between very tight and very weak bonding. Each deletion of a positive charge reduced the thermal denaturation temperature (Tm) by approximately 5 degrees C. Mismatches in the DNA oligomers reduced the Tm values by 3 to 5 degrees C for each of the DNGU oligomers. DNGUs were found to bind in a 2:1 fashion to complimentary DNA in the same manner as DNG. 相似文献
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Oligodeoxynucleic acid (21-mer) containing both negatively charged phosphate and positively charged ribonucleic guanidine linkages (RNG/DNA chimera) have been synthesized. DNA binding characteristics and nuclease resistance of RNG/DNA chimeras have been evaluated. Using the bcr-abl oncogene (cause of chronic myeloid leukemia) as a target, the binding of a 21-mer RNG/DNA chimera that includes six RNG's is more than 103.5 stronger than the binding of 21-mer composed solely of DNA. 相似文献
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Molecular dynamics simulations employing a molecular mechanics (MM) force field and hybrid quantum mechanics (QM) and MM (QM/MM) have been carried out to investigate the product specificity and mechanism of the histone H4 lysine 20 (H4-K20) methylation by human histone lysine methyltransferase SET8. At neutral pH, the target lysine is available to only the enzyme in the protonated state. The first step in the methylation reaction must be deprotonation of the lysine target which is followed by the (+)AdoMet methylation of the neutral lysine [Enz.Lys-CH(2)-NH(3)(+).(+)AdoMet --> H(+) + Enz.Lys-CH(2)-NH(2).(+)AdoMet -->--> Enz.Lys-CH(2)-N(Me)H(2)(+).AdoHcy]. The electrostatic interactions between two positive charges on (+)AdoMet and Lys20-NH(3)(+) decrease the pK(a) of Lys20-NH(3)(+). Upon formation of Enz.Lys-NH(3)(+).(+)AdoMet, a water channel by which the proton escapes to the outer solvent phase is formed. The formation of a water channel for the escape of a proton from Lys20-N(Me)H(2)(+) in Enz.Lys20-N(Me)H(2)(+).(+)AdoMet is not formed because the methyl substituent blocks the starting of the water channel. Thus, a second methylation does not take place. The dependence of the occurrence of methyl transfer on the formation of a water channel in SET8 is in accord with our previous reports on product specificity by histone lysine monomethyltransferase SET7/9, large subunit lysine dimethyltransferase (LSMT), and viral histone lysine trimethyltransferase (vSET). The average value of the experimental DeltaG(E)() for the six lysine methyl transfer reactions catalyzed by vSET, LSMT, and SET7/9 with p53 as a substrate is 22.1 +/- 1.0 kcal/mol, and the computed average (DeltaG(C)()) is 22.2 +/- 0.8 kcal/mol. In this study, the computed free energy barrier of the methyl transfer reaction [Lys20-NH(2) + (+)AdoMet --> Lys20-N(Me)H(2)(+) + AdoHcy] catalyzed by SET8 is 20.8 kcal/mol. This is in agreement with the value of 20.6 kcal/mol calculated from the experimental rate constant (0.43 +/- 0.02 min(-1)). Our bond-order computations establish that the H4-K20 monomethylation in SET8 is a concerted linear S(N)2 displacement reaction. 相似文献
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A new type of microgonotropen that fluoresces upon binding to dsDNA has been synthesized. FMGT-1, an analogue of the minor groove binder Hoechst 33258, is functionalized with a polyamine chain capable of interacting with the phosphate backbone of DNA. Binding studies indicate that FMGT-1 binds more tightly to dsDNA than the parent compound Hoechst 33258. 相似文献
10.
Recent advances in computational methods and the availability of fast, affordable computers have made the modeling of enzymatic reactions practical. The remaining challenges include achieving the accuracy level at which thermodynamic parameters and kinetic constants for different substrates, mutant enzymes, or in the presence of allosteric effectors can be predicted quantitatively. 相似文献