The stability of Seeman JX DNA topoisomers of paranemic crossover (PX) molecules as a function of crossover number.

We use molecular dynamics simulations in explicit water and salt (Na+) to determine the effect of varying the number of crossover points on the structure and stability of the PX65 paranemic crossover DNA molecule and its JXM topoisomers (M denotes the number of missing crossover points), recently synthesized by the Seeman group at New York University. We find that PX65, with six crossover points, is the most stable, and that the stability decreases monotonically with the number of crossover points PX65 > JX1 > JX2 > JX3 > JX4, with 6, 5, 4, 3 and 2 crossover points, respectively. Thus, for PX65/JX1, the strain energy is approximately 3 kcal/mol/bp, while it is approximately 13 kcal/mol/bp for JX2, JX3 and JX4. Another measure of the stability is the change in the structure from the minimum energy structure to the equilibrium structure at 300 K, denoted as root-mean-square deviation in coordinates (CRMSD). We find that CRMSD is approximately 3.5 A for PX65, increases to 6 A for JX1 and increases to 10 A for JX2/JX3/JX4. As the number of crossover points decreases, the distance between the two double helical domains of the PX/JX molecules increases from approximately 20 A for PX65 to 23 A for JX4. This indicates that JX2, JX3 and JX4 are less likely to form, at least in with Na+. However, in all the cases, the two double helical domains have average helicoidal parameters similar to a typical B-DNA of similar length and base sequence.

[1]  A. Turberfield,et al.  A DNA-fuelled molecular machine made of DNA , 2022 .

[2]  T. Darden,et al.  Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems , 1993 .

[3]  C. S. Tung,et al.  Nucleic acid modeling tool (NAMOT): an interactive graphic tool for modeling nucleic acid structures , 1994, Comput. Appl. Biosci..

[4]  T. Darden,et al.  Toward the Accurate Modeling of DNA: The Importance of Long-Range Electrostatics , 1995 .

[5]  N C Seeman,et al.  Two Dimensions and Two States in DNA Nanotechnology , 2000, Journal of biomolecular structure & dynamics.

[6]  N. Seeman,et al.  Design and self-assembly of two-dimensional DNA crystals , 1998, Nature.

[7]  N. Seeman,et al.  A robust DNA mechanical device controlled by hybridization topology , 2002, Nature.

[8]  N. Seeman,et al.  A nanomechanical device based on the B–Z transition of DNA , 1999, Nature.

[9]  J. Reif,et al.  Construction, analysis, ligation, and self-assembly of DNA triple crossover complexes , 2000 .

[10]  P. Kollman,et al.  A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules , 1995 .

[11]  N. Seeman.  DNA in a material world , 2003, Nature.

[12]  T Schlick,et al.  A-Tract bending: insights into experimental structures by computational models. , 2000, Journal of molecular biology.

[13]  Phiset Sa-Ardyen,et al.  The flexibility of DNA double crossover molecules. , 2003, Biophysical journal.

[14]  R Lavery,et al.  The definition of generalized helicoidal parameters and of axis curvature for irregular nucleic acids. , 1988, Journal of biomolecular structure & dynamics.

[15]  DNA Based Computers, Proceedings of a DIMACS Workshop, New Brunswick, New Jersey, USA, June 14-15, 1999 , 2000, DNA Based Computers.

[16]  M Feig,et al.  Structural equilibrium of DNA represented with different force fields. , 1998, Biophysical journal.

[17]  N. Seeman.  DNA Nicks and Nodes and Nanotechnology , 2001 .

[18]  L M Adleman,et al.  Molecular computation of solutions to combinatorial problems. , 1994, Science.

[19]  Lloyd M. Smith,et al.  DNA computing on surfaces , 2000, Nature.

[20]  R. Osman,et al.  Computational Simulations of DNA Distortions by a cis,syn-Cyclobutane Thymine Dimer Lesion† , 1996 .

[21]  N. Seeman,et al.  DNA double-crossover molecules. , 1993, Biochemistry.

[22]  Sharon Brunett,et al.  Molecular dynamics for very large systems on massively parallel computers: The MPSim program , 1997 .

[23]  T. Darden,et al.  Accurate crystal molecular dynamics simulations using particle-mesh-Ewald: RNA dinucleotides — ApU and GpC , 1995 .

[24]  N. Seeman,et al.  Paranemic crossover DNA: a generalized Holliday structure with applications in nanotechnology. , 2004, Journal of the American Chemical Society.

[25]  L. Li,et al.  Molecular dynamics simulations of the d(CCAACGTTGG)(2) decamer: influence of the crystal environment. , 2000, Biophysical journal.

[26]  T. Darden,et al.  A smooth particle mesh Ewald method , 1995 .

[27]  N. Seeman.  Biochemistry and structural DNA nanotechnology: an evolving symbiotic relationship. , 2003, Biochemistry.

[28]  G. Ciccotti,et al.  Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes , 1977 .

[29]  Jean-Louis Mergny,et al.  DNA duplex–quadruplex exchange as the basis for a nanomolecular machine , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Kent R. Wilson,et al.  Thermodynamics and quantum corrections from molecular dynamics for liquid water , 1982 .