Bending of DNA by Asymmetric Charge Neutralization: All-Atom Energy Simulations
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- 作者：Konstantin M. Kosikov ; Andrey A. Gorin ; Xiang-Jun Lu ; Wilma K. Olson ; and Gerald S. Manning
- 刊名：Journal of the American Chemical Society
- 出版年：2002
- 出版时间：May 1, 2002
- 年：2002
- 卷：124
- 期：17
- 页码：4838 - 4847
- 全文大小：377K
- 年卷期：v.124,no.17(May 1, 2002)
- ISSN：1520-5126
文摘
DNA dodecamers of the alternating d(CG)·d(CG) sequence with six phosphate groups eithercharge-neutralized or substituted by neutral methylphosphonates across the major or minor groove havebeen subjected to energy minimization to determine the conformational effect of the asymmetric eliminationof phosphate charge. We report bending angles, directions of bending, and detailed structural characteristicssuch as groove widths and local base-pair parameters. Our principal results are that charge neutralizationon one face of the DNA induces significant bending toward the neutralized face, in agreement with theoreticalpredictions on a simplified model and experimental data on a similar base-pair sequence, and that theDNA conformation averaged over all stereospecific methylphosphonate substitutions is nearly the sameas the conformation produced by charge neutralization of the phosphates. Individual isomers, however,cover a wide range of structures, with the magnitude and direction of overall bending sensitive to the precisestereochemical pattern of neutralization. Our simulation does not explicitly contain counterions, and theresults therefore suggest that counterions can influence DNA structure by neutralizing the phosphate charge.These data provide new hints into the molecular mechanisms which underlie the deformations of DNAstructure induced by the binding of positively charged proteins and other tightly associated cationic species.