The role of molecular structure of sugar‐phosphate backbone and nucleic acid bases in the formation of single‐stranded and double‐stranded DNA structures

Our previous DFT computations of deoxydinucleoside monophosphate complexes with Na⁺‐ions (dDMPs) have demonstrated that the main characteristics of Watson‐Crick (WC) right‐handed duplex families are predefined in the local energy minima of dDMPs. In this work, we study the mechanisms of contribution of chemically monotonous sugar‐phosphate backbone and the bases into the double helix irregularity. Geometry optimization of sugar‐phosphate backbone produces energy minima matching the WC DNA conformations. Studying the conformational variability of dDMPs in response to sequence permutation, we found that simple replacement of bases in the previously fully optimized dDMPs, e.g. by constructing Pyr‐Pur from Pur‐Pyr, and Pur‐Pyr from Pyr‐Pur sequences, while retaining the backbone geometry, automatically produces the mutual base position characteristic of the target sequence. Based on that, we infer that the directionality and the preferable regions of the sugar‐phosphate torsions, combined with the difference of purines from pyrimidines in ring shape, determines the sequence dependence of the structure of WC DNA. No such sequence dependence exists in dDMPs corresponding to other DNA conformations (e.g., Z‐family and Hoogsteen duplexes). Unlike other duplexes, WC helix is unique by its ability to match the local energy minima of the free single strand to the preferable conformations of the duplex. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 640–650, 2014.     

Interaction of cyclic cytosine-, guanine-, thymine-, uracil- and mixed guanine-cytosine base tetrads with K+, Na+ and Li+ ions -- a density functional study

We have carried out B3LYP hybrid density functional studies of complexes formed by cyclic cytosine-, guanine-, thymine-, uracil- and mixed guanine cytosine-tetrads with Li+, Na+ and K+ ions to determine their structures and interaction energies. The conformations studied have been restricted to a hydrogen bond pattern closely related to the tetrads observed in experimental nucleic acid structures. A comparison of the alkali metal ion/tetrad complexes with the tetrads without cations indicates that alkali metal ions modulate the tetrad structures significantly and that even the hydrogen bond pattern may change. Guanine-tetrad cation complexes show the strongest interaction energy compared to other tetrads that occur less frequently in experimental structures. The most stable G-tetrad/metal ion structure adopts a nearly planar geometry that is especially suitable for tetraplex formation, which requires approximately parallel tetrad planes. In the cytosine-tetrad there is a very large central cavity suitable for cation recognition, but the complexes adopt a non-planar structure unsuitable for stacking, except possibly for ions with very large radii. Uracil and thymine tetrads show a significant different characteristics which may contribute to the differences between DNA and RNA     

Simulation of interactions between nucleic acid bases by refined atom-atom potential functions

Energy of interaction between nitrogen bases of nucleic acid has been calculated as a function of parameters determining the mutual position of two bases. Refined atom-atom potential functions are suggested. These functions contain terms proportional to the first (electrostatics), sixth (or tenth for the atoms forming a hydrogen bond) and twelfth (repulsion of all atoms) powers of interatomic distance. Calculations have shown that there are two groups of minima of the base interaction energy. The minima of the first group correspond to coplanar arrangement of the base pairs and hydrogen bond formation. The minima of the second group correspond to the position of bases one above the other in almost parallel planes. There are 28 energy minima corresponding to the formation of coplanar pairs with two (three for the G:C pair) almost linear N-H . . . O and (or) N-H . . . N hydrogen bonds. The position of nitrogen bases paired by two such H-bonds in any crystal of nucleic acid component in polynucleotide complexes and in tRNA is close to the position in one of these minima. Besides, for each pair there are energy minima corresponding to the formation of a single N-H . . . O or N-H . . . N and one C-H . . . O or C-H . . . N hydrogen bond. The form of potential surface in the vicinity of minima has been characterized. The results of calculations agree with the experimental data and with more rigorous calculations based on quantum-mechanical approach.     

Simulation of Interactions between Nucleic Acid Bases by Refined Atom-Atom Potential Functions

Abstract

Energy of interaction between nitrogen bases of nucleic acids has been calculated as a function of parameters determining the mutual position of two bases. Refined atom-atom potential functions are suggested. These functions contain terms proportional to the first (electrostatics), sixth (or tenth for the atoms forming a hydrogen bond) and twelfth (repulsion of all atoms) powers of interatomic distance. Calculations have shown that there are two groups of minima of the base interaction energy. The minima of the first group correspond to coplanar arrangement of the base pairs and hydrogen bond formation. The minima of the second group correspond to the position of bases one above the other in almost parallel planes. There are 28 energy minima corresponding to the formation of coplanar pairs with two (three for the G:C pair) almost linear N-H … O and (or) N-H … N hydrogen bonds. The position of nitrogen bases paired by two such H-bonds in any crystal of nucleic acid component, in polynucleotide complexes and in tRNA is close to the position in one of these minima. Besides, for each pair there are energy minima corresponding to the formation of a single N-H … O or N-H … N and one C-H … O or C-H … N hydrogen bond. The form of potential surface in the vicinity of minima has been characterized. The results of calculations agree with the experimental data and with more rigorous calculations based on quantum- mechanical approach.     

Simulation of conformational possibilities of DNA via calculation of nonbonded interactions of complementary dinucleoside phosphate complexes

Using classical potential functions, we carried out potential-energy calculations on the complementary deoxydinucleoside phosphate complexes dApdA:dUpdU, dUpdA:dUpdA, and dApdU:dApdU. All dihedral and bond angles, except those of the nitrogen bases, were varied. The resulting minimum-energy conformations of the complexes are close to DNA A- and B-family conformations, with a typical arrangement of the nitrogen bases. The dihedral and bond angles of one of the molecules forming the complex can thereby differ by several degrees from those of the other molecule. For different base sequences, some dihedral and bond angles may vary over a range of several degrees without appreciably changing the total energy of the complex. Some low-energy conformations of the complexes corresponding to other regions of the conformational space are also found. The biological consequences of possible changes in dihedral and bond angles, occurring on interaction with other molecules, are discussed.     

Nmr studies of the molecular conformations in the linear oligopeptides H-(L-Ala)n-L-Pro-OH

The molecular conformations of the linear oligopeptides H-(L -Ala)_n-L -Pro-OH, with n = 1,2 and 3, have been investigated. ¹³C nmr observation of the equilibrium between the cis and trans forms of the Ala-Pro peptide bond indicated the occurrence of nonrandom conformations in solutions of these flexible peptides. The formation of the nonrandom species containing the cis form of the Ala-Pro bond was found to depend on the deprotonation of the carboxylic acid group of proline, the solvent, and the ionic strength in aqueous solution. The influence of intramolecular hydrogen bonding on the relative conformational energies of the species containing the cis and trans Ala-Pro peptide bond was studied by comparison of the peptides H-(Ala)_n-Pro-OH with analogous molecules where hydrogen bond formation was excluded by the covalent structure. In earlier work a hydrogen bond between the protonated terminal carboxylic acid group and the carbonyl oxygen of the penultimate amino acid residue had been suggested to stabilize conformations including trans proline. For the systems described here this hypothesis can be ruled out, since the cis:trans ratio is identical for molecules with methyl ester protected and free protonated terminal carboxylic acid groups of proline. Direct evidence for hydrogen bond formation between the deprotonated terminal carboxylic acid group and the amide proton of the penultimate amino acid residue in the molecular species containing cis proline was obtained from ¹H nmr studies. However, the cis:trans ratio of the Ala-Pro bond was not affected by N-methylation of the penultimate amino acid residue, which prevents formation of this hydrogen bond. Overall the experimental observations lead to the conclusion that the relative energies of the peptide conformations including cis or trans proline are mainly determined by intramolecular electrostatic interactions, whereas in the molecules considered, intramolecular hydrogen bonding is a consequence of specific peptide backbone conformations rather than a cause for the occurrence of energetically favored species. Independent support for this conclusion was obtained from model consideration which indicated that electrostatic interactions between the terminal carboxylic acid group and the carbonyl oxygen of the penultimate amino acid residue could indeed account for the observed relative conformational energies of the species containing cis and trans proline, respectively.     

Simulation of interactions in the co-planar nucleic acid base pairs using atom-atom potential functions

Calculations of the energy of nucleic acid base interactions as a function of parameters determining mutual position of two bases in a plane have been performed. Atom-atom potential functions used include terms proportional to the first (electrostatic), sixth (or tenth for the atoms of hydrogen bond) and 12th power of interatomic distance. The calculations have shown the existence of 27 energy minima which correspond to the formation of co-planar pairs with two (or three for G : C pair) almost linear N--H...O and N--H...N hydrogen bonds. The positions of nitrogen bases bound by two hydrogen bonds in every crystal of nucleic acid components, in the complexes of polynucleotides and in tRNA are near to the positions in one of these minima. In addition for every pair there exist energy minima which correspond to the formation of one N--H...O or N--H...N and one C--H...O or C--H...N hydrogen bond. Energy behavior near minima have been investigated. The results of our calculations are in agreement with experimental data and with the calculations which employ quantum mechanical results.     

Binding of sulfonamide and acetamide to the active-site Zn2+ in carbonic anhydrase: a theoretical study

Self-consistent field molecular orbital (SCF MO) calculations at both 4-31G and STO-3G levels have been used to examine the binding conformations of sulfonamide and acetamide compounds to the active site of carbonic anhydrase. The results are as follows: (1) sulfonamide binds to the Zn2+ ion in its deprotonated form through the sulfonamide nitrogen to the fourth coordination site of the metal ion; (2) acetamide as neutral species binds to the basic form of the enzyme through the carbonyl oxygen to the fifth coordination site of the metal ion; and (3) the acetamidate ion binds to the acid form of the enzyme through the amide nitrogen to form a tetracoordinated metal complex with three histidine ligands. Analysis of the effects of individual active-site residues on the binding conformations of these inhibitors suggests that metal alone favors bidentate coordination of sulfonamidate and acetamidate complexes and that electron donation from three histidine ligands to the metal ion determines the formation of a tetracoordinated metal complex, which is further stabilized by the presence of Thr 199, as it receives one hydrogen bond from the sulfonamide NH- or from the acetamide NH- and donates a backbone NH hydrogen bond to a sulfonamide oxygen. The calculated binding conformation of sulfonamide and the hydrogen-bonding interactions between sulfonamide and the enzyme are consistent with the X-ray diffraction study of the AMSulf-HCA II complex. However, no X-ray structures are available for amide-HCA II complexes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Structure calculations for single-stranded DNA complexed with the single-stranded DNA binding protein GP32 of bacteriophage T4: a remarkable DNA structure

In this study it is established by calculation which regular conformations single-stranded DNA and RNA can adopt in the complex with the single-stranded DNA binding protein GP32 of bacteriophage T4. In order to do so, information from previous experiments about base orientations and the length and diameter of the complexes is used together with knowledge about bond lengths and valence angles between chemical bonds. It turns out that there is only a limited set of similar conformations which are in agreement with experimental data. The arrangement of neighboring bases is such that there is ample space for aromatic residues of the protein to partly intercalate between the bases, which is in agreement with a previously proposed model for the binding domain of the protein [Prigodich, R. V., Shamoo, Y., Williams, K. R., Chase, J. W., Konigsberg, W. H., & Coleman, J. E. (1986) Biochemistry 25, 3666-3671]. Both C2'endo and C3'endo sugar conformations lead to calculated DNA conformations that are consistent with experimental data. The orientation of the O2' atoms of the sugars in RNA can explain why the binding affinity of GP32 for polyribonucleotides is lower than for polydeoxyribonucleotides.     

Stereochemistry of ATP and GTP bound to fish haemoglobins. A transferred nuclear overhauser enhancement, 31P-nuclear magnetic resonance, oxygen equilibrium and molecular modelling study

This study was undertaken in order to test the models of ATP and GTP binding to carp deoxyhaemoglobin proposed by Perutz & Brunori (1982) and to find out why GTP is a more potent allosteric effector than ATP. We have determined the conformations of both nucleoside triphosphates by nuclear magnetic resonance studies and found them to be the same. The purines are in anti conformation about the glycosidic bond that links them to the ribose; the pentose ring is 3'-endo; the P-O5'-C5'-C4' torsion angle lies in the trans domain (180 degrees +/- 20 degrees); the P alpha-O-P beta and P beta-O-P gamma angles are as in the free nucleotides, i.e. the trinucleotide chain is fully extended. Models having this conformation were fitted, first manually and then by energy refinement, to the effector site of an atomic model of human deoxyhaemoglobin in which the side-chains in the NA, EF and H segments had been replaced by those of carp. The results showed the location of the polar groups in carp haemoglobin to be such that (PO4) gamma can accept hydrogen bonds from Val NA1 beta 2 and from Arg H21 beta 1, while (PO4) beta and (PO4) alpha can accept hydrogen bonds from Lys EF6 beta 1 and beta 2. In ATP, the 6-amino group of the purine can donate a hydrogen bond to Glu NA2 beta 1. In GTP, the 2-amino group can donate a hydrogen bond to Glu NA2 beta 1; in addition, Val Na1 beta 1 can donate a hydrogen bond to O2' of the ribose. This additional hydrogen bond may explain why in carp haemoglobin GTP is a stronger allosteric effector than ATP. We have found the influence of the two allosteric effectors on the oxygen affinity of trout IV haemoglobin to be the same, even though the only difference in the lining of the allosteric effector sites lies in the replacement of Glu Na2 beta in carp by Asp in trout IV haemoglobin. Model building then showed that formation of a hydrogen bond between Asp Na2 beta and the 2-amino group of guanine precludes formation of a hydrogen bond between Val NA1 beta and O2' of the ribose or vice versa, which makes the number of hydrogen bonds formed between trout IV haemoglobin and GTP the same as those formed with ATP.     

Synthesis, X-ray crystallographic structures of thio substituted N-acetyl N'-methylamide alanine and evaluation of sp sulfur parameters of the CFF91 force field.

Acetyl thioalanine N-methyl (Ac-Alat-NHMe) and thioacetyl alanine N-methyl (Act-Ala-NHMe) were synthesized, crystallized and their X-ray diffraction structures determined for the first time. Both molecules adopted beta-sheet conformations and showed similar hydrogen bonding patterns with one molecular surface forming two oxo hydrogen bonds and the other forming two thio hydrogen bonds. The crystal structure data for the two thioamides provided a validation of the thioamide parameters for the newly derived CFF91 force field because the observed crystal (phi, psi) angles were situated in the global minimum regions of the theoretical (phi, psi) map predicted using the parameters. In addition, the parameters were further validated because conformational energy minimization of the crystal structure produced low deviations in unit cell dimensions, bond lengths, bond angles and torsional angles, and a 120-ps molecular dynamics simulation also gave a low deviation for the most probable N-H...S=C bond distance.     

Interaction of Cyclic Cytosine-, Guanine-, Thymine-, Uracil- and Mixed Guanine-Cytosine Base Tetrads with K+, Na+ and Li+ Ions—A Density Functional Study

Abstract

We have carried out B3LYP hybrid density functional studies of complexes formed by cyclic cytosine-, guanine-, thymine-, uracil- and mixed guanine cytosine-tetrads with Li⁺, Na⁺ and K⁺ ions to determine their structures and interaction energies. The conformations studied have been restricted to a hydrogen bond pattern closely related to the tetrads observed in experimental nucleic acid structures. A comparison of the alkali metal ion/tetrad complexes with the tetrads without cations indicates that alkali metal ions modulate the tetrad structures significantly and that even the hydrogen bond pattern may change. Guanine-tetrad cation complexes show the strongest interaction energy compared to other tetrads that occur less frequently in experimental structures. The most stable G-tetrad/metal ion structure adopts a nearly planar geometry that is especially suitable for tetraplex formation, which requires approximately parallel tetrad planes. In the cytosine-tetrad there is a very large central cavity suitable for cation recognition, but the complexes adopt a non-planar structure unsuitable for stacking, except possibly for ions with very large radii. Uracil and thymine tetrads show a significant different characteristics which may contribute to the differences between DNA and RNA.     

Effect of microsolvation on zwitterionic glycine: an ab initio and density functional theory study

The effect of microsolvation on zwitterionic glycine, considering both (-NH3(+)) as proton donor and (-COO(-)) as proton acceptor at correlated ab initio (MP2) level and density functional methods (B3LYP, PW91, MPW1PW91 and PBE) using 6-311++G** basis set has been reported. DFT methods have been employed so as to compare the performance/quality of different gradient-corrected correlation functionals (PW91, PBE), hybrid functionals (B3LYP, MPW1PW91) and to predict the near quantitative structural and vibrational properties, at reduced computational cost. B3LYP method outperforms among the different DFT methods for the computed hydrogen bond distances and found closer to the value obtained by correlated MP2 level, whereas MPW1PW91 and PBE methods shows very similar values but approximately 0.03 A less, compared to B3LYP method. MP2 calculation and single point CCSD(T)//MP2 calculation have been considered to decompose the interaction energy, including corrections for basis set superposition error (BSSE). Moreover, charge distribution analysis has also been carried out to understand the long raised questions, how and why the two body energies have significant contribution to the total binding energy.     

Models for the 3(10)-helix/coil,pi-helix/coil,and alpha-helix/3(10)-helix/coil transitions in isolated peptides.

Models for the 3(10)-helix/coil and pi-helix/coil equilibria have been derived. The theory is based on classifying residues into helical or nonhelical (coil) conformations. Statistical weights are assigned to residues in a helical conformation with an associated helical hydrogen bond, a helical conformation with no hydrogen bond, an N-cap position, a C-cap position, or the reference coil conformation. The models for alpha-helix formation and 3(10)-helix formation have also been combined to describe a three-state equilibrium in which alpha-helical, 3(10)-helical, and coil conformations are populated. The results are compared with the modified Lifson-Roig theory for the alpha-helix/coil equilibrium. The comparison accounts for the experimental observations that 3(10)-helices tend to be short and pi-helices are not favored for any length. This work may provide a framework for quantitatively rationalizing experimental work on isolated 3(10)-helices and mixed 3(10)-/alpha-helices.     

The nucleation of monomeric parallel beta-sheet-like structures and their self-assembly in aqueous solution

The aromatic diacid residue 4,6-dibenzofuranbispropionic acid (1) was designed to nucleate a parallel beta-sheet-like structure in small peptides in aqueous solution via a hydrogen-bonded hydrophobic cluster. Even though a 14-membered ring hydrogen bond necessary for parallel beta-sheet formation is favored in simple amides composed of 1, this hydrogen bonding interaction does not appear to be sufficient to nucleate parallel beta-sheet formation in the absence of hydrophobic clustering between the dibenzofuran portion of 1 and the hydrophobic side chains of the flanking alpha-amino acids. The subsequence --hydrophobic residue-1-hydrophobic residue-- is required for folding in the context of a nucleated two-stranded parallel beta-sheet structure. In all cases where the peptidomimetics can fold into two diastereomeric parallel beta-sheet structures having different hydrogen bonding networks, these conformations appear to exchange rapidly. The majority of the parallel beta-sheet structures evaluated herein undergo linked intramolecular folding and self-assembly, affording a fibrillar beta-sheet quaternary structure. To unlink folding and assembly, asymmetric parallel beta-sheet structures incorporating N-methylated alpha-amino acid residues have been synthesized using a new solid phase approach. Residue 1 facilitates the folding of several peptides described within affording a monomeric parallel beta-sheet-like structure in aqueous solution, as ascertained by a variety of spectroscopic and biophysical methods, increasing our understanding of parallel beta-sheet structure.     

Possible configuration of dimers of Gua-Cyt bases. Computation by molecular mechanic models and density functional theory

The energies of interactions between guanine and cytosine in various mutual positions were calculated by the methods of molecular mechanics with refined atom-atom potential functions and the quantum mechanics theory of density functional. Both methods indicate three types of mutual positions of bases in local energy minima. These types correspond to (1) nearly coplanar base positions with intermolecular hydrogen bond formation (base pairing); (2) arrangements of two bases in nearly parallel planes one above another (base stacking); and (3) nearly perpendicular positions of base planes. According to the calculations, the global energy minimum corresponds to the Watson-Crick base pair with three hydrogen bonds. A specific feature of the pair is a transition from many positions of type (2) to positions of type (1) without any energy barrier. This feature is revealed by both methods. Another special feature of this pair is a deviation, for most of mutual base positions, of the amine group atoms from the ring plane, the deviation being more pronounced for Gua. These features are important for understanding the conformational behavior of DNA fragments and the RNA structure.     

The beginning and the end: flanking nucleotides induce a parallel G-quadruplex topology

Genomic sequences susceptible to form G-quadruplexes (G4s) are always flanked by other nucleotides, but G4 formation in vitro is generally studied with short synthetic DNA or RNA oligonucleotides, for which bases adjacent to the G4 core are often omitted. Herein, we systematically studied the effects of flanking nucleotides on structural polymorphism of 371 different oligodeoxynucleotides that adopt intramolecular G4 structures. We found out that the addition of nucleotides favors the formation of a parallel fold, defined as the ‘flanking effect’ in this work. This ‘flanking effect’ was more pronounced when nucleotides were added at the 5′-end, and depended on loop arrangement. NMR experiments and molecular dynamics simulations revealed that flanking sequences at the 5′-end abolish a strong syn-specific hydrogen bond commonly found in non-parallel conformations, thus favoring a parallel topology. These analyses pave a new way for more accurate prediction of DNA G4 folding in a physiological context.     

1H and 15N NMR investigation of the interaction of pyrimidine nucleotides with ribonuclease A

Extensive 1H and 15H NMR investigations of the nucleotide moieties capable of hydrogen bonding to ribonuclease A were carried out in order to gain more detailed information on the specificity of nucleotide-enzyme interaction. The 1H investigations focussed on those protons presumed to be involved in hydrogen bonding between the various nucleotides and the enzyme. In particular these were the imino protons of the uridine nucleotides and the amino protons of the cytidine nucleotides. The technique of 15N-1H double quantum filtering was applied for observation of the resonances of the latter in the nucleotide-enzyme complex. The downfield shift observed for the imino proton resonance of the uridine nucleotides was indicative of hydrogen bond formation to the enzyme. 15N NMR spectra of the free nucleotides and the nucleotide-enzyme complexes were also acquired to examine the possibility of hydrogen bond formation at the N3 site of both pyrimidine bases and the amino group of the cytidine nucleotides. The downfield shift observed for the 15N3 resonance of the uridine nucleotides and the upfield shift observed for the corresponding resonance of the cytidine nucleotides was evidence that the N3 moiety acts as hydrogen donor or hydrogen acceptor in the nucleotide-enzyme complex. The effect of complex formation on the 15N1 resonance of the respective bases was also studied. Both 1H and 15N NMR results indicated subtle differences between the complexes of the 2' and 3' nucleotides. The extent of hydrogen bonding as well as the arrangement of the nucleotide base at the active site of the enzyme varies in dependence on the position of the phosphate group. It is established that hydrogen bonding, though not the main binding force between the nucleotides and the enzyme, is certainly a major factor of RNase A specificity for pyrimidine nucleotides.     

Dissecting the protein-RNA interface: the role of protein surface shapes and RNA secondary structures in protein-RNA recognition

Protein-RNA interactions are essential for many biological processes. However, the structural mechanisms underlying these interactions are not fully understood. Here, we analyzed the protein surface shape (dented, intermediate or protruded) and the RNA base pairing properties (paired or unpaired nucleotides) at the interfaces of 91 protein-RNA complexes derived from the Protein Data Bank. Dented protein surfaces prefer unpaired nucleotides to paired ones at the interface, and hydrogen bonds frequently occur between the protein backbone and RNA bases. In contrast, protruded protein surfaces do not show such a preference, rather, electrostatic interactions initiate the formation of hydrogen bonds between positively charged amino acids and RNA phosphate groups. Interestingly, in many protein-RNA complexes that interact via an RNA loop, an aspartic acid is favored at the interface. Moreover, in most of these complexes, nucleotide bases in the RNA loop are flipped out and form hydrogen bonds with the protein, which suggests that aspartic acid is important for RNA loop recognition through a base-flipping process. This study provides fundamental insights into the role of the shape of the protein surface and RNA secondary structures in mediating protein-RNA interactions.     

Analysis of conformational parameters in nucleic acid fragments. II. Co-crystal complexes of nucleic acid bases.

Studies have been made of conformational parameters in co-crystal complexes and compounds of nucleic acid bases in which there is the possibility of formation of hetero-base-pairs. Using published data extracted from the Cambridge structural database, a total of 37 base-pairs were found, of which 25 were hetero-pairs and 12 homo-pairs. These base-pairs were subject to analysis to reveal hydrogen bond parameters, propeller twist, buckle and C1'-C1' separation (or a similar parameter if C1' atoms were not present). Hetero-pairs were found to show larger twists than homo-pairs, the magnitude of twist being unrelated to hydrogen bond parameters or buckle value. The propeller twisting is less pronounced in these nucleic acid bases than in nucleosides, but still has a significant magnitude. Propeller twisting in hetero-pairs is found to be larger than in homo-pairs. Hetero-pairs appear to be formed preferentially in competitive situations.