Hydrogen-atom abstraction from the adenine-uracil base pair

The hydrogen-abstracted radicals from the adenine-uracil (AU) base pair have been studied at the B3LYP/DZP++ level of theory. The A(N9)-U and A-U(N1) radicals, which correspond to hydrogen-atom abstraction at the adenine N9 and uracil N1 atoms, respectively, were predicted to be the two lowest-lying among the nine (AU-H) radicals studied in this study. The removal of the amino hydrogen of the adenine moiety that forms a hydrogen bond with the uracil O4 atom in the AU pair resulted in radical A(N6a)-U, which has the smallest base-pair dissociation energy, 5.9 kcal mol(-1). This radical is more likely to dissociate into the two isolated bases than to recover the hydrogen bond with the O4 atom through N6-H bond rotation along the C6-N6 bond. In general, the radicals generated by C-H bond breaking were higher in energy than those arising from N-H bond cleavage, because the unpaired electrons in the carbon-centered radicals were mainly localized on the carbon atom from which the hydrogen atom was removed. However, the highest-lying radical was found to arise from removal of the N3 hydrogen of uracil. The most remarkable structural feature of this radical is a very short C-H...O distance of 2.094 A, consistent with a substantial hydrogen bond. Although this radical lost the N1...H-N3 hydrogen bond between the two bases, its dissociation energy was predicted to be 12.9 kcal mol(-1), similar to that of the intact AU base pair. This is due to the transfer of electron density from the adenine N1 atom to the uracil N3 atom.     

Structures and energetics of the deprotonated adenine-uracil base pair, including proton-transferred systems

The B3LYP/DZP++ level of theory has been employed to investigate the structures and energetics of the deprotonated adenine-uracil base pairs, (AU-H)-. Formation of the lowest-energy structure, [A(N9)-U]- (which corresponds to deprotonation at the N9 atom of adenine), through electron attachment to the corresponding neutral is accompanied by proton transfer from the uracil N3 atom to the adenine N1 atom. The driving force for this proton transfer is a significant stabilization from the base pairing in the proton transferred form. Such proton transfer upon electron attachment is also observed for the [A(N6b)-U]- and [A(C2)-U]- anions. Electron attachment to the A-U(N3) radical causes strong lone pair repulsion between the adenine N1 and the uracil N3 atoms, driving the two bases apart. Similarly, lone pair repulsion in the anion A(N6a)-U causes the loss of coplanarity of the two base units. The computed adiabatic electron attachment energies for nine AU-H radicals range from 1.86 to 3.75 eV, implying that the corresponding (AU-H)- anions are strongly bound. Because of the large AEAs of the (AU-H) radicals, the C-H and N-H bond dissociation in the AU- base pair anions requires less energy than the neutral AU base pair. The computed C-H and N-H bond dissociation energies for the AU- anion (i.e., the AU base pair plus one electron) are in the range 1.0-3.2 eV, while those for neutral AU are 4.08 eV or higher.     

Adiabatic electron affinities of the polyhydrated adenine-thymine base pair: a density functional study

Adiabatic electron affinities (AEAs) of the adenine-thymine (AT) base pair surrounded by 5 and 13 water molecules have been studied by density functional theory (DFT). Geometries of neutral AT x nH2O and anionic (AT x nH2O)- complexes (n = 5 and 13) were fully optimized, and vibrational frequency analysis was performed at the B3LYP/6-31+G** level of theory. The optimized structures of the neutral (AT x nH2O) and (AT x nH2O)- complexes were found to be somewhat nonplanar. Some of the water molecules are displaced away from the AT ring plane and linked with one another by hydrogen bonds. The optimized structures of the complexes are found to be in a satisfactory agreement with the observed experimental and molecular dynamics simulation results. In the optimized anionic complexes, the thymine (T) moiety was found to be puckered, whereas the adenine (A) moiety remained almost planar. Natural population analysis (NPA) performed using the B3LYP/6-31+G** method shows that the thymine moiety in the anionic (AT x nH2O)- complexes (n = 5 and 13) has most of the excess electronic charge, i.e., approximately -0.87 and approximately -0.81 (in the unit of magnitude of the electronic charge), respectively. The zero-point energy corrected adiabatic electron affinities of the hydrated AT base pair were found to be positive both for n = 5 and 13 and have the values of 0.97 and 0.92 eV, respectively, which are almost three times the AEA of the AT base pair. The results show that the presence of water molecules appreciably enhances the EA of the base pair.     

Marked influences on the adenine-cytosine base pairs by electron attachment and ionization

The reverse wobble and the reverse Hoogsteen adenine-cytosine mispairs regarding their radical cations and anions are studied with the hybrid three-parameter B3LYP density functional method and 6-31+G(d), 6-311+G(2df,2p) basis sets. Hydrogen bonding mispairs are remarkably influenced by electron attachment and ionization. Only one stronger hydrogen bond N6-H (in adenine)...N3 (in cytosine) exists in the radical pair, while the strengths of two N-H...N hydrogen bonds in the neutral pair are comparable. Geometrical coplanarity is found for the neutral and cationic pairs, in contrast to the anionic pairs in which the cytosine moiety exhibits significant deformation due to electron attachment. Dissociation energies for the neutral and radical pairs are slightly higher than those of the adenine-thymine pairs but much smaller than those of the guanine-cytosine pairs. Valence-bound anions of these two adenine-cytosine pairs are thermodynamically stable by 0.1-0.2 eV with respect to the neutral pairs. On the basis of the comparison between the experimental data of the solvated clusters and the calculated values, these two pairs can be quantitatively equivalent to the clusters in which each base is solvated by five water molecules.     

Density functional study toward understanding dehydrogenation of the adenine-thymine base pair and its anion

The dehydrogenated radicals and anions of Watson-Crick adenine-thymine (A-T) base pair have been investigated by the B3LYP/DZP++ approach. Calculations show that the dehydrogenated radicals and anions have relatively high stabilities compared with the single base adenine and thymine. The electron attachment to the A-T base pair and its derivatives significantly modifies the hydrogen bond interactions and results in remarkable structural changes. As for the dehydrogenated A-T radicals, they have relatively high electron affinities and different dehydrogenation properties with respect to their constituent elements. The relatively low-cost hydrogen eliminations correspond to the (N9)-H (adenine) and (N1)-H (thymine) bonds cleavage. Both dehydrogenation processes have Gibbs free energies of reaction DeltaG degrees of 13.4 and 17.2 kcal mol-1, respectively. The solvent water exhibits significant effect on electron attachment and dehydrogenation properties of the A-T base pair and its derivatives. In the dehydrogenating process, the anionic A-T fragment gradually changes its electronic configuration from pi* to sigma* state, like the single bases adenine and thymine.     

Microsolvation effect, hydrogen-bonding pattern, and electron affinity of the uracil-water complexes U-(H2O)n (n = 1, 2, 3)

To achieve a systematic understanding of the influence of microsolvation on the electron accepting behaviors of nucleobases, the reliable theoretical method (B3LYP/DZP++) has been applied to a comprehensive conformational investigation on the uracil-water complexes U-(H(2)O)(n) (n = 1, 2, 3) in both neutral and anionic forms. For the neutral complexes, the conformers of hydration on the O2 of uracil are energetically favored. However, hydration on the O4 atom of uracil is more stable for the radical anions. The electron structure analysis for the H-bonding patterns reveal that the CH...OH(2) type H-bond exists only for di- and trihydrated uracil complexes in which a water dimer or trimer is involved. The electron density structure analysis and the atoms-in-molecules (AIM) analysis for U-(H(2)O)(n) suggest a threshold value of the bond critical point (BCP) density to justify the CH...OH(2) type H-bond; that is, CH...OH(2) could be considered to be a H-bond only when its BCP density value is equal to or larger than 0.010 au. The positive adiabatic electron affinity (AEA) and vertical detachment energy (VDE) values for the uracil-water complexes suggest that these hydrated uracil anions are stable. Moreover, the average AEA and VDE of U-(H(2)O)(n) increase as the number of the hydration waters increases.     

Microhydration of cytosine and its radical anion: cytosine.(H2O)n (n=1-5)

Microhydration effects on cytosine and its radical anion have been investigated theoretically, by explicitly considering various structures of cytosine complexes with up to five water molecules. Each successive water molecule (through n=5) is bound by 7-10 kcal mol(-1) to the relevant cytosine complex. The hydration energies are uniformly higher for the analogous anion systems. While the predicted vertical detachment energy (VDE) of the isolated cytosine is only 0.48 eV, it is predicted to increase to 1.27 eV for the lowest-lying pentahydrate of cytosine. The adiabatic electron affinity (AEA) of cytosine was also found to increase from 0.03 to 0.61 eV for the pentahydrate, implying that the cytosine anion, while questionable in the gas phase, is bound in aqueous solution. Both the VDE and AEA values for cytosine are smaller than those of uracil and thymine for a given hydration number. These results are in qualitative agreement with available experimental results from photodetachment-photoelectron spectroscopy studies of Schiedt et al. [Chem. Phys. 239, 511 (1998)].     

Electron affinities of small uracil-water complexes: a comparison of benchmark CCSD(T) calculations with DFT

We present benchmark CCSD(T) calculations of the adiabatic electron affinities (AEA) and the vertical detachment energies (VDE) of the uracil molecule interacting with one to three water molecules. Calculations with rather large aug-cc-pVTZ basis set were only tractable when the space of virtual orbitals was reduced to about 60% of the full space employing the OVOS (Optimized Virtual Orbital Space) technique. Because of the microhydration, the valence-bound uracil anion is stabilized leading to gradually more positive values of both AEA and VDE with increasing number of participating water molecules. This agrees with experimental findings. Upon hydration by three water molecules, the electron affinity of uracil increased in comparison with AEA of the isolated molecule by about 250 up to 570 meV, depending on the geometry of the complex. CCSD(T) results confirm trends determined by DFT calculations of the microhydrated uracil and its anion, even if electron affinities of the free and hydrated uracil molecule are overestimated by DFT by up to 300 meV.     

Effects of microsolvation on uracil and its radical anion: uracil(H2O)n (n = 1-5)

Microsolvation effects on the stabilities of uracil and its anion have been investigated by explicitly considering the structures of complexes of uracil with up to five water molecules at the B3LYPDZP++ level of theory. For all five systems, the global minimum of the neutral cluster has a different equilibrium geometry from that of the radical anion. Both the vertical detachment energy (VDE) and adiabatic electron affinity (AEA) of uracil are predicted to increase gradually with the number of hydrating molecules, qualitatively consistent with experimental results from a photodetachment-photoelectron spectroscopy study [J. Schiedt et al., Chem. Phys. 239, 511 (1998)]. The trend in the AEAs implies that while the conventional valence radical anion of uracil is only marginally bound in the gas phase, it will form a stable anion in aqueous solution. The gas-phase AEA of uracil (0.24 eV) was higher than that of thymine by 0.04 eV and this gap was not significantly affected by microsolvation. The largest AEA is that predicted for uracil(H2O)5, namely, 0.96 eV. The VDEs range from 0.76 to 1.78 eV.     

Structural and energetic characterization of a DNA nucleoside pair and its anion: deoxyriboadenosine (dA)-deoxyribothymidine (dT)

The geometries of the DNA nucleoside pairs between 2'-deoxyriboadenosine (dA) and 2'-deoxyribothymidine (dT) and its anion (dAdT-) were fully optimized using carefully calibrated density functional methods. The addition of an electron to dAdT results in remarkable changes to the two hydrogen bonding distances, the H...O distance decreasing by 0.303 angstroms and the N...H distance increasing by 0.229 angstroms. The electron affinity of the dAdT pair was studied to reveal the correct trends of adiabatic electron affinity (EA(ad)) under the influence of the additional components to the individual bases. The consequence of negative charge in terms of structural variations, energetic changes, and charge distribution were explored. The EA(ad) of dAdT is predicted to be positive (0.60 eV), and it exhibits a substantial increase compared with those of the corresponding bases A and T and the nucleic acid base pair AT. The effects of pairing and the addition of the sugar moiety on the EA(ad) are well described as the summation of the individual influences. The influence of the pairing on the EA is comparable to that of the addition of 2-deoxyribose. The excess charge is mainly located on the thyminyl moiety in the anionic dAdT pair. The positive vertical electron affinity (VEA = 0.20 eV) for dAdT suggests that it is able to form a stable anion through electron attachment. A large vertical detachment energy (VDE = 1.14 eV) has been determined for the anionic dAdT nucleoside pair. Therefore, one may expect that the stable anionic dAdT nucleoside pair should be able to undergo the subsequent glycosidic bond cleavage process.     

Adenine–Au and adenine–uracil–Au. Non-conventional hydrogen bonds of the anions and donator–acceptor properties of the neutrals

This is a study of adenine–Au and adenine–uracil–Au (neutral, anionic and cationic), applying the B3LYP density-functional approach. In these systems, the interaction is directly related to the charge; so that as the metal atomic charge increases, the bond strength also increases. Neutral molecules are weakly bonded, the interaction in the case of cations is mainly electrostatic and in the case of the anions, the extra electron is localized on the metal atom and consequently, non-conventional hydrogen bonds are formed. In the case of adenine–Au (anion), the H dissociation energy is similar to the electron dissociation energy, and therefore both reactions may be possible. Moreover, the Au anionic atom modifies the hydrogen bonds of the uracil–adenine base pair. This may be significant in the study of point mutations that may occur in the Watson–Crick dimmer of nucleic basis. The electron-donator properties of these compounds are analyzed with the aid of the donator–acceptor map (DAM), previously described. Adenine–Au, uracil–Au and adenine–uracil–Au are more effective electron donors, but poorer electron acceptors than adenine, uracil and adenine–uracil. If the electron acceptor properties of carotenoids such as β-carotene and astaxanthin are compared, there are indications that astaxanthin may act as an oxidant instead of an antioxidant with the uracil–adenine base pair. The oxidation of nucleic acid bases by carotenoids may have important consequences, as oxidative damage of DNA and RNA appears to be linked to cancer. This is something that demands further studies and for this reason, work concerning the reactivity of carotenoids with DNA-nitrogen bases is in progress.     

Vertical detachment energies of anionic thymidine: Microhydration effects

Density functional theory has been employed to investigate microhydration effects on the vertical detachment energy (VDE) of the thymidine anion by considering the various structures of its monohydrates. Structures were located using a random searching procedure. Among 14 distinct structures of the anionic thymidine monohydrate, the low-energy structures, in general, have the water molecule bound to the thymine base unit. The negative charge developed on the thymine moiety increases the strength of the intermolecular hydrogen bonding between the water and base units. The computed VDE values of the thymidine monohydrate anions are predicted to range from 0.67 to 1.60 eV and the lowest-energy structure has a VDE of 1.32 eV. The VDEs of the monohydrates of the thymidine anion, where the N(1)[Single Bond]H hydrogen of thymine has been replaced by a 2(')-deoxyribose ring, are greater by ～0.30?eV, compared to those of the monohydrates of the thymine anion. The results of the present study are in excellent agreement with the accompanying experimental results of Bowen and co-workers [J. Chem. Phys. 133, 144304 (2010)].     

Interligand interactions controlling the mu-N7,N9-metal bonding of adenine (AdeH) to the N-benzyliminodiacetato(2-) copper(II) chelate and promoting the N9 versus N3 tautomeric proton transfer: molecular and crystal structure of [Cu2(NBzIDA)(2)(H2O)(2)(mu-N7,N9-Ade(N3)H)].(3)H2O

The reaction in water of the N-benzyliminodiacetate-copper(II) chelate ([Cu(NBzIDA)]) and the adenine:thymine base pair complex (AdeH:ThyH) with a Cu/NBzIDA/AdeH/ThyH molar ratio of 2:2:1:1 yields [Cu(2)(NBzIDA)(2)(H(2)O)(2)(mu-N7,N9-Ade(N3)H)].3H(2)O and free ThyH. The compound has been studied by thermal, spectral, and X-ray diffraction methods. In the asymmetric dinuclear complex units both Cu(II) atoms exhibit a square pyramidal coordination, where the four closest donors are supplied by NBzIDA in a mer-tridentate conformation and the N7 or N9 donors of AdeH, which is protonated at N3. The mu-N7,N9 bridge represents a new coordination mode for nonsubstituted AdeH, except for some adeninate(1-)-[methylmercury(II)] derivatives studied earlier. The dinuclear complex is stabilized by the Cu-N7 and Cu-N9 bonds and N6-H(exocyclic)...O(carboxyl) and N3-H(heterocyclic)...O(carboxyl) interligand interactions, respectively. The structure of the new compound differs from that of the mononuclear compound [Cu(NBzIDA)(Ade(N9)H)(H(2)O)].H(2)O, in which the unusual Cu-N3(AdeH) bond is stabilized by a N9-H...O(carboxyl) interligand interaction and where alternating benzyl-AdeH intermolecular pi,pi-stacking interactions produce infinite stacked chains. The possibility for ThyH to be involved in the molecular recognition between [Cu(NBzIDA)] and the AdeH:ThyH base pair is proposed.     

Photoelectron spectrum of valence anions of uracil and first-principles calculations of excess electron binding energies

The photoelectron spectrum (PES) of the uracil anion is reported and discussed from the perspective of quantum chemical calculations of the vertical detachment energies (VDEs) of the anions of various tautomers of uracil. The PES peak maximum is found at an electron binding energy of 2.4 eV, and the width of the main feature suggests that the parent anions are in a valence rather than a dipole-bound state. The canonical tautomer as well as four tautomers that result from proton transfer from an NH group to a C atom were investigated computationally. At the Hartree-Fock and second-order Moller-Plesset perturbation theory levels, the adiabatic electron affinity (AEA) and the VDE have been converged to the limit of a complete basis set to within +/-1 meV. Post-MP2 electron-correlation effects have been determined at the coupled-cluster level of theory including single, double, and noniterative triple excitations. The quantum chemical calculations suggest that the most stable valence anion of uracil is the anion of a tautomer that results from a proton transfer from N1H to C5. It is characterized by an AEA of 135 meV and a VDE of 1.38 eV. The peak maximum is as much as 1 eV larger, however, and the photoelectron intensity is only very weak at 1.38 eV. The PES does not lend support either to the valence anion of the canonical tautomer, which is the second most stable anion, and whose VDE is computed at about 0.60 eV. Agreement between the peak maximum and the computed VDE is only found for the third most stable tautomer, which shows an AEA of approximately -0.1 eV and a VDE of 2.58 eV. This tautomer results from a proton transfer from N3H to C5. The results illustrate that the characteristics of biomolecular anions are highly dependent on their tautomeric form. If indeed the third most stable anion is observed in the experiment, then it remains an open question why and how this species is formed under the given conditions.     

Microsolvation pattern of the hydrated radical anion of uracil: U-(H2O)n (n = 3-5)

The microsolvation patterns of the uracil radical anion in water clusters U-(H2O)n with n ranging from 3 to 5 were investigated by the density functional theory approach. The electron detachment energies (VDE) of the stable anionic complexes with different numbers of hydration water are predicted. The linear dependence of the VDE value of the most stable anionic complexes with respect to the hydration number suggests the importance of the clustered waters in the microsolvation of the radical anion of the nucleobases. The formation of the water clusters is found to be necessary in the most stable conformers of the tri-, tetra-, and pentahydrated radical anion of uracil. The microsolvation pattern with three or more well-separated hydration water molecules in the first hydration layer is less stable than the arrangement with the waters in tight clusters. The charge transfer between the anionic uracil and the hydration water is high. Good agreement between the experimental and the theoretical vertical detachment energy yield in this study further demonstrates the practicability of the B3LYP/DZP++ approach in the study of radical anions of the DNA subunits.     

Theoretical studies on photoelectron and IR spectral properties of Br2.-(H2O)n clusters

We report vertical detachment energy (VDE) and IR spectra of Br2.-.(H2O)n clusters (n=1-8) based on first principles electronic structure calculations. Cluster structures and IR spectra are calculated at Becke's half-and-half hybrid exchange-correlation functional (BHHLYP) with a triple split valence basis function, 6-311++G(d,p). VDE for the hydrated clusters is calculated based on second order Moller-Plesset perturbation (MP2) theory with the same set of basis function. On full geometry optimization, it is observed that conformers having interwater hydrogen bonding among solvent water molecules are more stable than the structures having double or single hydrogen bonded structures between the anionic solute, Br2.-, and solvent water molecules. Moreover, a conformer having cyclic interwater hydrogen bonded network is predicted to be more stable for each size hydrated cluster. It is also noticed that up to four solvent H2O units can reside around the solute in a cyclic interwater hydrogen bonded network. The excess electron in these hydrated clusters is localized over the solute atoms. Weighted average VDE is calculated for each size (n) cluster based on statistical population of the conformers at 150 K. A linear relationship is obtained for VDE versus (n+3)(-1/3) and bulk VDE of Br2.- aqueous solution is calculated as 10.01 eV at MP2 level of theory. BHHLYP density functional is seen to make a systematic overestimation in VDE values by approximately 0.5 eV compared to MP2 data in all the hydrated clusters. It is observed that hydration increases VDE of bromine dimer anion system by approximately 6.4 eV. Calculated IR spectra show that the formation of Br2.--water clusters induces large shifts from the normal O-H stretching bands of isolated water keeping bending modes rather insensitive. Hydrated clusters, Br2.-.(H2O)n, show characteristic sharp features of O-H stretching bands of water in the small size clusters.     

CRYSTAL STRUCTURE OF A NEW STEROIDAL ALKALOID FROM PEIMINE,C_(27)H_(43)NO_2·H_2O

<正> Mr = 431,.6 orthorhombic,P212121,a = 8.526(2), b = 9.970(2), c= 29.787(6)X,Z=4,V=2532.0A3,Dc=1.132g.cm-3,λ(MoKα)=0.71073A,μ=0.67cm-1, F(000) = 952, final R= 0.069 for 1733 observed reflections with I>1σ(I). All six-membered rings in this free base are in the chair form and the five-membered ring C takes the envelope conformation, with the ring fusions A/B traps, B/C trans, C/D cis, D/E trans and E/F trans. There is one crystal water whose oxygen atom joins the adjacent alkaloid molecules by the inter-molecular hydrogen bonds O(1)-H... 0(3)-H(31)...0(2)=C(6). Pertinent parameters for the hydrogen bonding system are: .0(1)...0(3) 2.878(6), 0(2)...O(3) 2.917(6)A,O(1)-H...O(3) 178.3(3)°,and 0(3)-H(31)...0(2) 165.6(3)°.     

H-bonding patterns in the platinated guanine-cytosine base pair and guanine-cytosine-guanine-cytosine base tetrad: an electron density deformation analysis and AIM study

The atoms in molecule theory (AIM) and electronic structure analysis are applied together to investigate H-bonding patterns in metalated nucleobase complexes. The influence of Pt on the intra GC base pair H-bonding has been found to reduce intra base pair H-bonding of N4(C)...O6(G) in the platinated GC pair and GCGC tetrad. The relaxation of geometry constrains in metalated nucleobases is found to be decisively important in the formation of novel molecular architectures from nucleobases and metal entities. The incorporation of the platinum in the GCGC tetrad benefits the formation of the unique CH...N (H5(C)...N1(G)) hydrogen bond pattern in the tetrad by offering improved geometric constraints rather than through changing the electronic properties around the H5(C) and N1(G) sites. Platination at the N7 of guanine reduces the deprotonation energy considerably.     

Theoretical studies on interactions between low energy electrons and protein-DNA fragments: valence anions of AT-amino acids side chain complexes

Electron attachment to trimeric complexes that mimic most frequent hydrogen bonding interactions between an amino acid side chain (AASC) and the Watson-Crick (WC) 9-methyladenine-1-methylthymine (MAMT) base pair has been studied at the B3LYP/6-31++G(d,p) level of theory. Although the neutral trimers will not occur in the gas phase due to unfavorable free energy of stabilization (G(stab)) they should form a protein-DNA complex where entropy changes related to formation of such a complex will more than balance its disadvantageous G(stab). The most stable neutrals possess an identical pattern of hydrogen bonds (HBs). In addition, the proton-acceptor (N7) and proton-donor (N10) atoms of adenine involved in those HBs are located in the main groove of DNA. All neutral structures support the adiabatically stable valence anions in which the excess electron is localized on a π* orbital of thymine. The vertical detachment energies (VDEs) of anions corresponding to the most stable neutrals are substantially smaller than that of the isolated WC MAMT base pair. Hence, electron transfer from the anionic thymine to the phosphate group and as a consequence formation of a single strand break (SSB) should proceed more efficiently in a protein-dsDNA complex than in the naked dsDNA as far as electron attachment to thymine is concerned.     

Theoretical studies on the interaction of proteins with base pairs. I. Ab initio calculation for the effect of H-bonding interaction of proteins on the stability of adenine–uracil pair

The hydrogen-bonding interaction of protein with the adenine–uracil base pair was investigated by the ab initio MO method (STO -3G level). We found that the stability of the base pair was greatly affected by the hydrogen-bonding interaction of several residues of protein in different ways, depending on whether the interacting species is charged or neutral, whether the interaction is made from the major groove or minor groove side, and which of the two, adenine or uracil, is hydrogen bonded. These results were interpreted as the cooperative interaction between the base pair hydrogen bonds and external ones. The implications of the present results to biological functions were also discussed.