Topic
Guanine
About: Guanine is a research topic. Over the lifetime, 9418 publications have been published within this topic receiving 345853 citations. The topic is also known as: Gua & 2-amino-6-oxopurine.
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TL;DR: The previously discovered linear relation between the base composition of DNA, expressed in percentage of guanine plus cytosine bases, and the denaturation temperature, T m, has been further investigated and it appears that the measurement of the T m is a satisfactory means of determining base composition in DNA.
Abstract: The previously discovered linear relation between the base composition of DNA, expressed in terms of percentage of guanine plus cytosine bases, and the denaturation temperature, T m , has been further investigated. By means of measurements on 41 samples of known base composition the previously observed relation has been confirmed. It can be summarized thus : for a solvent containing 0·2 M -Na + , T m = 69·3 + 0·41 (G-C) where T m is in degrees Centigrade and G-C refers to the mole percentage of guanine plus cytosine. The deviations of experimental points from this relation are no more than that expected from the uncertainties of base analysis and the variations of a half degree in the reproducibility of determining the T m . Consequently it appears that the measurement of the T m is a satisfactory means of determining base composition in DNA. The T m values are most simply measured by following the absorbance at 260 m μ as a function of temperature of the DNA solution and noting the midpoint of the hyperchromic rise. Only 10 to 50 μ g of DNA are required. A number of other DNA samples of unknown base composition have been examined in this manner and their base compositions recorded.
4,154 citations
TL;DR: An all atom potential energy function for the simulation of proteins and nucleic acids and the first general vibrational analysis of all five nucleic acid bases with a molecular mechanics potential approach is presented.
Abstract: We present an all atom potential energy function for the simulation of proteins and nucleic acids. This work is an extension of the CH united atom function recently presented by S.J. Weiner et al. J. Amer. Chem. Soc., 106, 765 (1984). The parameters of our function are based on calculations on ethane, propane, n−butane, dimethyl ether, methyl ethyl ether, tetrahydrofuran, imidazole, indole, deoxyadenosine, base paired dinucleoside phosphates, adenine, guanine, uracil, cytosine, thymine, insulin, and myoglobin. We have also used these parameters to carry out the first general vibrational analysis of all five nucleic acid bases with a molecular mechanics potential approach.
3,291 citations
TL;DR: In this article, an approach for deriving net atomic charges from ab initio quantum mechanical calculations using a least squares fit of the quantum mechanically calculated electrostatic potential to that of the partial charge model is presented.
Abstract: We present an approach for deriving net atomic charges from ab initio quantum mechanical calculations using a least squares fit of the quantum mechanically calculated electrostatic potential to that of the partial charge model. Our computational approach is similar to those presented by Momany [J. Phys. Chem., 82, 592 (1978)], Smit, Derissen, and van Duijneveldt [Mol. Phys., 37, 521 (1979)], and Cox and Williams [J. Comput. Chem., 2, 304 (1981)], but differs in the approach to choosing the positions for evaluating the potential. In this article, we present applications to the molecules H2O, CH3OH, (CH3)2O, H2CO, NH3, (CH3O)2PO, deoxyribose, ribose, adenine, 9-CH3 adenine, thymine, 1-CH3 thymine, guanine, 9-CH3 guanine, cytosine, 1-CH3 cytosine, uracil, and 1-CH3 uracil. We also address the question of inclusion of “lone pairs,” their location and charge.
2,976 citations
TL;DR: Adenine base editors (ABEs) that mediate the conversion of A•T to G•C in genomic DNA are described and a transfer RNA adenosine deaminase is evolved to operate on DNA when fused to a catalytically impaired CRISPR–Cas9 mutant.
Abstract: The spontaneous deamination of cytosine is a major source of transitions from C•G to T•A base pairs, which account for half of known pathogenic point mutations in humans. The ability to efficiently convert targeted A•T base pairs to G•C could therefore advance the study and treatment of genetic diseases. The deamination of adenine yields inosine, which is treated as guanine by polymerases, but no enzymes are known to deaminate adenine in DNA. Here we describe adenine base editors (ABEs) that mediate the conversion of A•T to G•C in genomic DNA. We evolved a transfer RNA adenosine deaminase to operate on DNA when fused to a catalytically impaired CRISPR-Cas9 mutant. Extensive directed evolution and protein engineering resulted in seventh-generation ABEs that convert targeted A•T base pairs efficiently to G•C (approximately 50% efficiency in human cells) with high product purity (typically at least 99.9%) and low rates of indels (typically no more than 0.1%). ABEs introduce point mutations more efficiently and cleanly, and with less off-target genome modification, than a current Cas9 nuclease-based method, and can install disease-correcting or disease-suppressing mutations in human cells. Together with previous base editors, ABEs enable the direct, programmable introduction of all four transition mutations without double-stranded DNA cleavage.
2,451 citations
TL;DR: It is shown that a protein nanopore with a covalently attached adapter molecule can continuously identify unlabelled nucleoside 5'-monophosphate molecules with accuracies averaging 99.8%.
Abstract: A single-molecule method for sequencing DNA that does not require fluorescent labelling could reduce costs and increase sequencing speeds. An exonuclease enzyme might be used to cleave individual nucleotide molecules from the DNA, and when coupled to an appropriate detection system, these nucleotides could be identified in the correct order. Here, we show that a protein nanopore with a covalently attached adapter molecule can continuously identify unlabelled nucleoside 5'-monophosphate molecules with accuracies averaging 99.8%. Methylated cytosine can also be distinguished from the four standard DNA bases: guanine, adenine, thymine and cytosine. The operating conditions are compatible with the exonuclease, and the kinetic data show that the nucleotides have a high probability of translocation through the nanopore and, therefore, of not being registered twice. This highly accurate tool is suitable for integration into a system for sequencing nucleic acids and for analysing epigenetic modifications. A protein nanopore with a permanent adaptor molecule can continuously identify unlabelled DNA bases with ∼99.8% accuracy. This level of performance could provide the foundation for the development of nanopore-based DNA sequencing technologies that are faster and less expensive than existing approaches.
1,783 citations