Monophosphate Complexes Research Articles

New Catalytic Residues and Catalytic Mechanism of the RNase T1 Family.

The ribonuclease T1 family, including RNase Po1 secreted by Pleurotus ostreatus, exhibits antitumor activity. Here, we resolved the Po1/guanosine-3'-monophosphate complex (3'GMP) structure at 1.75 Å. Structure comparison and fragment molecular orbital (FMO) calculation between the apo form and the Po1/3'GMP complex identified Phe38, Phe40, and Glu42 as the key binding residues. Two types of the RNase/3'GMP complex in RNasePo1 and RNase T1 were homologous to Po1, and FMO calculations elucidated that the biprotonated histidine on the β3 sheet (His36) on the β3 sheet and deprotonated Glu54 on the β4 sheet were advantageous to RNase activity. Moreover, tyrosine (Tyr34) on the β3 sheet was elucidated as a crucial catalytic residues. Mutation of Tyr34 with phenylalanine decreased RNase activity and diminished antitumor efficacy compared to that in the wild type. This suggests the importance of RNase activity in antitumor mechanisms.

Structural Bases for the Synergistic Inhibition of Human Thymidylate Synthase and Ovarian Cancer Cell Growth by Drug Combinations.

Simple SummaryDrug combinations may help overcome drug resistance, a relevant cause of failure of ovarian cancer therapy. However, designing successful combinations requires a lengthy preclinical validation process. We have analyzed combinations of 5-fluorouracil and raltitrexed, two anticancer drugs that target thymidylate synthase, a key enzyme for the nucleotide synthesis. We have observed administration sequence specific and synergistic combined effects of the two drugs against cisplatin sensitive and resistant ovarian cancer cells. However, the focus of this work was to show that a high stability of the complex of the enzyme with the two drugs, as highlighted by X-ray crystallography, and synergistic inhibition of the enzyme represent indicators, if not prerequisites, for this drug combination to be synergistically active against sensitive and resistant ovarian cancer cells. We thus propose that structural and mechanistic information acquired during the preclinical research can help predict a successful therapeutic application of a drug combination.Combining drugs represent an approach to efficiently prevent and overcome drug resistance and to reduce toxicity; yet it is a highly challenging task, particularly if combinations of inhibitors of the same enzyme target are considered. To show that crystallographic and inhibition kinetic information can provide indicators of cancer cell growth inhibition by combinations of two anti-human thymidylate synthase (hTS) drugs, we obtained the X-ray crystal structure of the hTS:raltitrexed:5-fluorodeoxyuridine monophosphate (FdUMP) complex. Its analysis showed a ternary complex with both molecules strongly bound inside the enzyme catalytic cavity. The synergistic inhibition of hTS and its mechanistic rationale were consistent with the structural analysis. When administered in combination to A2780 and A2780/CP ovarian cancer cells, the two drugs inhibited ovarian cancer cell growth additively/synergistically. Together, these results support the idea that X-ray crystallography can provide structural indicators for designing combinations of hTS (or any other target)-directed drugs to accelerate preclinical research for therapeutic application.

Binding Expedient of 2-carbamido-1,3-indandione to Nucleic Acids: Potential Fluorescent Probe.

Fluorescent and computational methods were used to elucidate the binding expedient of 2-carbamido-1,3-indandione (CAID) tautomers to nucleotides. The dependence of the fluorescence emission of CAID loaded nucleic acids sequences to compound concentration, temperature and time variation was investigated. It was found that the subject compound binds to nucleic acids but does not intercalate. According to our quantum-chemical calculations on the conjugation between CAID and nucleotides, the binding in the formed complexes may be through hydrogen bonds. Two possible types of complexes were considered-CAID to the phosphate group and CAID to the nucleobase. To estimate the binding affinity, the interaction energies of the formed complexes were calculated. Tautomer 2-carboamide-1-hydroxy-3-oxo-indane is preferred in the formation of complexes, and the phosphate group complexes were more stable. Generally, the guanosine and deoxyguanosine monophosphate complexes were the most preferred regardless of the complex type. Because of the lack of cytotoxic effect on untransformed cell lines of mouse embryo fibroblasts Balb/c 3T3 according to our previous report (Markova et al, (2017) Bulg Chem Commun, 49D, 221-226) and the affinity to nucleic acids, we can suggest that the subject compound could be suitable to be used as a novel type of fluorescent biomarker.

Thermal behavior of inosine 5′-monophosphate complexes with cobalt(II), nickel(II), copper(II) and cadmium(II) cations

Interaction of nucleotides and metals has been largely studied since they have biological importance. Divalent complexes of inosine 5'-monophosphate with cobalt(II) (IMP-Co), nickel(II) (IMP-Ni), copper(II) (IMP-Cu) and cadmium(II) (IMP-Cd) have been characterized by elemental analysis and submitted to thermogravimetry (TG), differential thermal analysis (DTA), differential scanning calorimetry (DSC) and thermogravimetry coupled to infrared spectroscopy (TG-FTIR). Cadmium(II) complex with inosine 5′-monophosphate had also its crystalline structure elucidated by single-crystal X-ray diffraction. Elemental analysis revealed that the isolated metal complexes presented a 1:1 stoichiometry. The thermal stability order was: IMP-Co (193 °C) = IMP-Cd (193 °C) < IMP-Ni (206 °C) < IMP-Cu (219 °C), after dehydration. Cd2+ ions present octahedral coordination with an IMP ligand through nitrogen donor atom and the remaining coordinating sites through five water molecules. The crystal packing assembly has a similar distribution to the DNA molecule, with alternation between the atoms leading to a helical conformation.

Synthesis and Biological Evaluations of a Novel Oxidovanadium(IV) Adenosine Monophosphate Complex as Anti-Diabetic Agent

In the present study, a novel [(AMP)(VO)(H2O)2] complex was formed through chemical reactions between oxidovanadium(IV)sulfate and adenosine monophosphate. This complex was characterized using various analyses, including microanalytical, molar conductivity, spectroscopic (solid reflectance and FTIR), magnetic susceptibility, thermogravimetric (TGA), X-ray powder diffraction (XRD), and scanning (SEM) and transmission (TEM) electron microscopy. The in vivo antidiabetic activity of the oxidovanadium(IV) complex was determined using streptozotocin-induced rats. The results suggested that the synthesized complex can be used as an antidiabetic agent based on the observed biochemical effects.

Supramolecular Assembly of Uridine Monophosphate (UMP) and Thymidine Monophosphate (TMP) with a Dinuclear Copper(II) Receptor.

Understanding the intermolecular interactions between nucleotides and artificial receptors is crucial to understanding the role of nucleic acids in living systems. However, direct structural evidence showing precise interactions and bonding features of a nucleoside monophosphate (NMP) with a macrocycle-based synthetic molecule has not been provided so far. Herein, we present two novel crystal structures of uridine monophosphate (UMP) and thymidine monophosphate (TMP) complexes with a macrocycle-based dinuclear receptor. Structural characterization of these complexes reveals that the receptor recognizes UMP through coordinate–covalent interactions with phosphates and π–π stackings with nucleobases and TMP through coordinate–covalent interactions with phosphate groups. Furthermore, the receptor has been shown to effectively bind nucleoside monophosphates in the order of GMP > AMP > UMP > TMP > CMP in water at physiological pH, as investigated by an indicator displacement assay.

Channeling of cAMP in PDE-PKA Complexes Promotes Signal Adaptation

Spatiotemporal control of the cAMP signaling pathway is governed by both hormonal stimulation of cAMP generation by adenylyl cyclases (activation phase) and cAMP hydrolysis by phosphodiesterases (PDEs) (termination phase). The termination phase is initiated by PDEs actively targeting the protein kinase A (PKA) R-subunit through formation of a PDE-PKAR-cyclic adenosine monophosphate (cAMP) complex (the termination complex). Our results using PDE8 as a model PDE, reveal that PDEs mediate active hydrolysis of cAMP bound to its receptor RIα by enhancing the enzymatic activity. This accelerated cAMP turnover occurs via formation of a stable PDE8-RIα complex, where the protein-protein interface forms peripheral contacts and the central ligand cements this ternary interaction. The basis for enhanced catalysis is active translocation of cAMP from its binding site on RIα to the hydrolysis site on PDE8 through direct “channeling.” Our results reveal cAMP channeling in the PDE8-RIα complex and a molecular description of how this channel facilitates processive hydrolysis of unbound cAMP. Thus, unbound cAMP maintains the PDE8-RIα complex while being hydrolyzed, revealing an undiscovered mode for amplification of PKA activity by cAMP-mediated sequestration of the R-subunit by PDEs. This novel regulatory mode explains the paradox of cAMP signal amplification by accelerated PDE-mediated cAMP turnover. This highlights how target effector proteins of small-molecule ligands can promote enzyme-mediated ligand hydrolysis by scaffolding effects. Enhanced activity of the PDE8-RIα complex facilitates robust desensitization, allowing the cell to respond to dynamic levels of cAMP rather than steady-state levels. The PDE8-RIα complex represents a new class of PDE-based complexes for specific drug discovery targeting the cAMP signaling pathway.

Iron Phosphate Catalyzed Asymmetric Cross-Dehydrogenative Coupling of 2-Naphthols with β-Ketoesters.

Chiral iron phosphate complexes were successfully exploited for asymmetric cross-dehydrogenative coupling reactions between 2-naphthols and β-ketoester derivatives. On the basis of kinetic studies, it is suggested that iron monophosphate complexes constitute the active catalysts that induce stereoselectivity during the carbon-carbon bond-formation step.

Analysis of the conformational features of Watson–Crick duplex fragments by molecular mechanics and quantum mechanics methods

It is generally accepted that the important characteristic features of the Watson-Crick duplex originate from the molecular structure of its subunits. However, it still remains to elucidate what properties of each subunit are responsible for the significant characteristic features of the DNA structure. The computations of desoxydinucleoside monophosphates complexes with Na-ions using density functional theory revealed a pivotal role of DNA conformational properties of single-chain minimal fragments in the development of unique features of the Watson-Crick duplex. We found that directionality of the sugar-phosphate backbone and the preferable ranges of its torsion angles, combined with the difference between purines and pyrimidines. in ring bases, define the dependence of three-dimensional structure of the Watson-Crick duplex on nucleotide base sequence. In this work, we extended these density functional theory computations to the minimal' fragments of DNA duplex, complementary desoxydinucleoside monophosphates complexes with Na-ions. Using several computational methods and various functionals, we performed a search for energy minima of BI-conformation for complementary desoxydinucleoside monophosphates complexes with different nucleoside sequences. Two sequences are optimized using ab initio method at the MP2/6-31++G** level of theory. The analysis of torsion angles, sugar ring puckering and mutual base positions of optimized structures demonstrates that the conformational characteristic features of complementary desoxydinucleoside monophosphates complexes with Na-ions remain within BI ranges and become closer to the corresponding characteristic features of the Watson-Crick duplex crystals. Qualitatively, the main characteristic features of each studied complementary desoxydinucleoside monophosphates complex remain invariant when different computational methods are used, although the quantitative values of some conformational parameters could vary lying within the limits typical for the corresponding family. We observe that popular functionals in density functional theory calculations lead to the overestimated distances between base pairs, while MP2 computations and the newer complex functionals produce the structures that have too close atom-atom contacts. A detailed study of some complementary desoxydinucleoside monophosphate complexes with Na-ions highlights the existence of several energy minima corresponding to BI-conformations, in other words, the complexity of the relief pattern of the potential energy surface of complementary desoxydinucleoside monophosphate complexes. This accounts for variability of conformational parameters of duplex fragments with the same base sequence. Popular molecular mechanics force fields AMBER and CHARMM reproduce most of the conformational characteristics of desoxydinucleoside monophosphates and their complementary complexes with Na-ions but fail to reproduce some details of the dependence of the Watson-Crick duplex conformation on the nucleotide sequence.

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.

Structure of the Pb²⁺-deprotonated dGMP complex in the gas phase: a combined MS-MS/IRMPD spectroscopy/ion mobility study.

The structure of the Pb(2+)-deprotonated 2'-deoxyguanosine-5'-monophosphate (dGMP) complex, generated in the gas phase by electrospray ionization, was examined by combining tandem mass spectrometry, mid-infrared multiple-photon dissociation (IRMPD) spectroscopy and ion mobility. In the gas phase, the main binding site of Pb(2+) onto deprotonated dGMP is the deprotonated phosphate group, but the question is whether an additional stabilization of the metallic complex can occur via participation of the carbonyl group of guanine. Such macrochelates indeed correspond to the most stable structures according to theoretical calculations. A multiplexed experimental approach was used to characterize the gas-phase conformation of the metallic complex and hence determine the binding mode of Pb(2+) with [dGMP](-). MS/MS analysis, observation of characteristic bands by IRMPD spectroscopy, and measurement of the ion mobility collision cross section suggest that gaseous [Pb(dGMP)-H](+) complexes adopt a macrochelate folded structure, which consequently differs strongly from the zwitterionic forms postulated in solution from potentiometric studies.

A new crystal form of human histidine triad nucleotide-binding protein 1 (hHINT1) in complex with adenosine 5'-monophosphate at 1.38 Å resolution.

Histidine triad nucleotide-binding protein 1 (HINT1) represents the most ancient and widespread branch of the histidine triad protein superfamily. HINT1 plays an important role in various biological processes and has been found in many species. Here, the structure of the human HINT1-adenosine 5'-monophosphate (AMP) complex at 1.38 Å resolution obtained from a new monoclinic crystal form is reported. The final structure has R(cryst) = 0.1207 (R(free) = 0.1615) and the model exhibits good stereochemical quality. Detailed analysis of the high-resolution data allowed the details of the protein structure to be updated in comparison to the previously published data.

Structural and Functional Characterization of Microcin C Resistance Peptidase MccF from Bacillus anthracis

Microcin C (McC) is heptapeptide adenylate antibiotic produced by Escherichia coli strains carrying the mccABCDEF gene cluster encoding enzymes, in addition to the heptapeptide structural gene mccA, necessary for McC biosynthesis and self-immunity of the producing cell. The heptapeptide facilitates McC transport into susceptible cells, where it is processed releasing a non-hydrolyzable aminoacyl adenylate that inhibits an essential aminoacyl-tRNA synthetase. The self-immunity gene mccF encodes a specialized serine peptidase that cleaves an amide bond connecting the peptidyl or aminoacyl moieties of, respectively, intact and processed McC with the nucleotidyl moiety. Most mccF orthologs from organisms other than E. coli are not linked to the McC biosynthesis gene cluster. Here, we show that a protein product of one such gene, MccF from Bacillus anthracis (BaMccF), is able to cleave intact and processed McC, and we present a series of structures of this protein. Structural analysis of apo-BaMccF and its adenosine monophosphate complex reveals specific features of MccF-like peptidases that allow them to interact with substrates containing nucleotidyl moieties. Sequence analyses and phylogenetic reconstructions suggest that several distinct subfamilies form the MccF clade of the large S66 family of bacterial serine peptidases. We show that various representatives of the MccF clade can specifically detoxify non-hydrolyzable aminoacyl adenylates differing in their aminoacyl moieties. We hypothesize that bacterial mccF genes serve as a source of bacterial antibiotic resistance.

Photosensitized electron transfer within a self-assembled norharmane–2′-deoxyadenosine 5′-monophosphate (dAMP) complex

Norharmane is a compound that belongs to a family of alkaloids called β-carbolines (βCs). These alkaloids are present in a wide range of biological systems, playing a variety of significant photo-dependent roles. Upon UV-A irradiation, βCs are able to act as efficient photosensitizers. In this work, we have investigated the photosensitized oxidation of 2'-deoxyadenosine 5'-monophosphate (dAMP) by norharmane in an aqueous phase, upon UV-A (350 nm) irradiation. The effect of the pH was evaluated on both the interactions between norharmane and dAMP in the ground and electronic excited states, and on the dAMP photosensitized oxidation. A quite strong static interaction between norharmane and dAMP was observed, especially under those pH conditions where the protonated form of the alkaloid is present (pH < 7). Theoretical studies were performed to further characterize the static complex structure. The participation of reactive oxygen species (ROS) in the photosensitized reaction was also investigated and the photoproducts were characterized by means of UV-LDI-MS and ESI-MS. All the data provided herein indicate that electron transfer (Type I) within a self-assembled norharmane-dAMP complex is the operative mechanism in the dAMP photosensitization.

Local structure around phosphorus and silicon in the CaO–SiO2–PO2.5 system

The local structure of phosphorus and silicon in the molten CaO–SiO2–PO2.5 slag system was investigated by magic angle spinning nuclear magnetic resonance (MAS-NMR). The 31P MAS-NMR spectra revealed that phosphorus was present primarily as the monophosphate complex ion PO43−, with a small amount of diphosphate ion also present. Their relative ratio to total phosphorus was independent of the phosphate concentration of the sample. In the case of the 29Si MAS-NMR, the mean number of the non-bridging oxygen atoms associated with tetrahedrally coordinated silicon decreased as the phosphate concentration increased at a fixed CaO/SiO2 ratio. This indicates that the nonbridging oxygen atoms around the silicon were replaced by bridging oxygen atoms around the phosphorus as the phosphate concentration in the samples increased.To elucidate the basicity dependence of the structure of slag, the relationship between the structure and optical basicity was also investigated. The relative ratio of Qn (Qn means the silicon atoms tetrahedrally bonded with “n” number of bridging oxygen atoms) strongly depends on the optical basicity. These optical basicity dependencies of the structures of phosphorus and silicon can be explained clearly by the basicity equalization concept (Duffy and Ingram, 1976) [12].

Direct Evidence for Tautomerization of the Uracil Moiety within the Pb2+/Uridine-5′-monophosphate Complex: A Combined Tandem Mass Spectrometry and IRMPD study

The structure of the [Pb(UMP)-H](+) (UMP = uridine-5'-monophosphate) complex was studied in the gas phase by combining electrospray ionization (ESI), tandem mass spectrometry, and mid-infrared multiple photon dissociation (IRMPD) spectroscopy. The results obtained show that Pb(2+) ions interact not only with the deprotonated phosphate group but also with a carbonyl group of the nucleobase moiety by folding of the mononucleotide, resulting in macrochelates that are not likely to be present in solution. Comparison between the IRMPD and DFT-computed spectra suggests that the ESI-generated complex likely corresponds to a mixture of several structures, and establishes the enolic tautomers as the most abundant species for the [Pb(UMP)-H](+) ion, while the very weak IRMPD signal observed at ∼1763 cm(-1) points to a minor population of oxo forms. Our data also suggest that losing the nucleobase residue under CID conditions does not necessarily mean a lack of interaction between the metal and the nucleobase moiety, as commonly reported in the literature for large oligonucleotides.

DFT study of DNA sequence dependence at the level of dinucleoside monophosphates

In this work we search for new energy minima of desoxydinucleoside monophosphate complexes with Na-ions (dDMPs) as the minimal fragments of DNA single strand via Density Functional Theory (DFT) computations and summarize our previous findings in this field. The analysis is illustrated by graphs of distribution of sugar-phosphate and glycosyl torsions as well as of sugar puckering for energy minima of various base sequences to elucidate the contributions of intra-strand interactions to DNA structure and polymorphism. Our recent computations revealed that the characteristic features of BI, BII, and AI families of DNA duplex conformations are initially predisposed in the dDMPs and namely in their local energy minima. New calculations and the analysis of our previous results enable us to verify and to draw conclusions about important role of sugar-phosphate backbone in the formation and sequence dependence of DNA duplexes. The optimized conformations of dDMPs with purine–purine and purine–pyrimidine sequences are characterized by substantial superposition of base rings whereas those with pyrimidine–pyrimidine and pyrimidine–purine sequences have small if any superposition. This result reveals itself as a universal rule for energy minima corresponding to all four families of right-handed duplexes with Watson–Crick base pairs (BI, BII, AI and AII). The character of base–base overlap is independent of the degree of variation of each of the backbone torsions, which may vary substantially or only slightly with the nucleoside sequence within a family. Computations on dDMP structures corresponding to duplexes with Hoogsteen pairs, started from the torsion angle values of the duplex, located characteristic energy minima for dApdT and dTpdA representative of this conformation. We observe that the rule of sequence dependence of base superposition does not apply to these systems. Biological consequences of existence of the obtained minima and the implications of the revealed regularities are discussed.

Structure of Pb2+/dCMP and Pb2+/CMP complexes as characterized by tandem mass spectrometry and IRMPD spectroscopy

The structure of Pb2+/cytidine-5′-monophosphate (CMP) and Pb2+/deoxycytidine-5′-monophosphate (dCMP) complexes were probed in the gas phase by combining electrospray ionization, tandem mass spectrometry and mid-infrared multiple-photon dissociation (IRMPD) spectroscopy. The fragment ions detected upon collision suggest that the metal interacts with both the phosphate group and the cytosine. This finding is further confirmed by IRMPD spectroscopy. The IRMPD spectrum of the ESI-generated [Pb(dCMP)−H]+ and [Pb(CMP)−H]+ complexes is indeed in very good agreement with DFT-computed infrared absorption spectra of macrochelate forms, in which the Pb2+ ion not only interacts with the phosphate group but also with the carbonyl group of the nucleobase moiety, by folding of the mononucleotides. The structures thus characterized therefore differ from those proposed in solution and deduced from potentiometric studies. Our data also suggest that losing the nucleobase residue under CID conditions does not necessarily mean a lack of interaction between the metal and the nucleobase moiety, as commonly mentioned in the literature for large oligonucleotides.

Nucleoside monophosphate complex structures of the endonuclease domain from the influenza virus polymerase PA subunit reveal the substrate binding site inside the catalytic center.

Highly pathogenic influenza virus strains currently in circulation pose a significant risk of a global pandemic. Following the reported crystal structure of the endonuclease domain from the avian influenza virus polymerase PA subunit, here we report the results of a systematic X-ray crystallographic analysis of its complex with adenosine, uridine, and thymidine nucleoside monophosphates (NMPs). Electron density corresponding to the monophosphate moiety of each nucleotide was apparent in each NMP complex and bound to the catalytic metal. A hydrophobic site was found to contribute to nucleoside binding. The NMP complex structures should represent the conformation of the bound product after nuclease cleavage. Moreover, one solvent molecule was found to occupy an equivalent position to the second reported Mn(2+) ion, where it mediates the interaction between bound NMPs and the N-terminal PA domain in the presence of the Mg(2+) ion. The results presented here indicate a possible cleavage mechanism and identify a distinct nucleotide binding pocket. The identification of this binding pocket opens a new avenue for anti-influenza drug discovery, targeting the cap-dependent endonuclease, in response to the worldwide threat of influenza.

DFT study of minimal fragments of nucleic acid single chain for explication of sequence dependence of DNA duplex conformation

DFT studies of desoxydinucleoside monophosphate complexes with Na-ions (dDMPs), using DGAUSS and ADF software reveal that the characteristic B-type conformation of DNA duplexes is initially predisposed in single strand in the form of a local minimum. Such predisposition may be important for biological functioning of DNA by facilitating an addition of new nucleotide in the processes of DNA duplication and restoration of double helix after unwinding. The computational results demonstrate the important contribution of intra-strand interactions to conformational stability and sequence-dependent variability of B-DNA duplexes. The main characteristics of the “canonical” BI conformations, such as the regions of torsion angles of sugar-phosphate backbone, C2′-endo or very close to C2′-endo sugar puckerings, and nearly parallel base-ring arrangements are already present in the single strand and are universal for all 16 dDMPs. The dihedral angle between the bases does not depend on the extent of their overlap, which suggests the major contribution of sugar-phosphate backbone to formation of these minima. The study reveals characteristic sequence dependence of the base arrangements. Namely, an extensive base-ring overlap takes place for all purine–purine and purine–pyrimidine sequences, and negligible ring overlap is observed in all pyrimidine–purine and pyrimidine–pyrimidine sequences. These arrangements closely resemble the geometrical characteristics of BI DNA in duplex crystals. Preliminary results of search for other energy minima related to helical DNA structures revealed the existence of BII-like minima for some dDMPs.