Book of Abstracts: Albany 2007
June 19-23 2007
Cross-correlations of base-pair and dimer step parameters of DNA
Deformability of both individual base pairs and dimer steps is important for DNA sequence recognition. Parameters describing base-pair and dimer step geometry may be correlated with each other due to stereochemical interactions of adjacent bases in dimer steps (e.g. as a way to relieve Calladine?s purine-purine clashes ). Moreover, distortions of base-pair geometry affect the reference frames used to calculate dimer parameters, resulting in appearance of intrinsic coupling between base-pair and dimer parameters . We systematically analyzed the cross-correlations of base-pair and dimer step parameters in 10 ns of unrestrained molecular dynamics simulation of four DNA dodecamers that comprise all 10 unique dimers. In addition to the previously observed intrinsic correlations , we report marked coupling for a number of base-pair and dimer step parameters including Propeller vs. Roll, Buckle vs. Tilt, Stagger vs. Rise, etc. Our results show that both differences and sums of base-pair parameters, which describe the successive residues forming a dimer step, may be strongly coupled to the dimer parameters of this step (illustrative schematics are shown in Figure 1). Furthermore, in many cases such coupling appears to be highly sequence dependent: e.g. sums of Propellers (Buckles) are positively correlated with Roll (Tilt) at purine-pyrimidine (RY) steps and negatively correlated at pyrimidine-purine (YR) steps. The sequence dependence of coupling may be underlain by the increased flexibility of pyrimidine as compared to purine nucleotides in each of the complementary pairs, which in turn is a result of the frequent sugar puckering switches in pyrimidines observed in our simulations. We hypothesize that the features of DNA conformational dynamics observed in our study could facilitate sequence recognition especially at the initial stages of the formation of protein-DNA complexes.
Yana V. Shashel
Department of Biological and Medical Physics, V. Karazin Kharkov National University, Kharkov, Ukraine
Figure 1. Examples of intrinsic coupling of base-pair and dimer step parameters. (A) Coupling of sum of Propellers with Roll at pyrimidine-purine (YR) step. Distortions of Propeller at the base pairs that form a dimer step result in non-zero Roll at this step. Note that Propeller values of the same sign appear at each base pair due to movement of pyrimidine bases (dark rectangles). (B), (C) Coupling of sum of Buckles with Tilt at purine-pyrimidine (RY) step and difference of Staggers with Rise at purine-purine (RR:YY) step.
References and Footnotes