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P Hobza

Publications and source records attributed to P Hobza.

At least 19 recordsLinked to original sources
PubMed2005

Structure and IR spectrum of phenylalanyl-glycyl-glycine tripetide in the gas-phase: IR/UV experiments, ab initio quantum chemical calculations, and molecular dynamic simulations.

We investigated the potential-energy surface (PES) of the phenylalanyl-glycyl-glycine tripeptide in the gas phase by means of IR/UV double-resonance spectroscopy, and quantum chemical and statistical thermodynamic calculations. Experimentally, we observed four conformational structures and we recorded their IR spectra in the spectral region of 3000-4000 cm(-1). Computationally, we investigated the PES by a combination of molecular dynamics/quenching procedures with high-level correlated ab initio calculations. We found that neither empirical potentials nor various DFT functionals provide satisfactory results. On the other hand, the approximative DFT method covering the dispersion energy yields a reliable set of the most stable structures, which we subsequently investigated with an accurate, correlated ab initio treatment. The global minimum contains three moderately strong intramolecular hydrogen bonds and is mainly stabilized by London dispersion forces between the phenyl ring, the carboxylic acid group, and various peptide bonds. A proper description of the last type of interaction requires accurate correlated ab initio calculations, including the complete basis set limit of the MP2 method and CCSD(T) correction terms. Since in our beam experiments the conformations are frozen by cooling from a higher temperature, it is necessary to localize the most stable structures on the free-energy surface rather than on the PES. We used two different procedures (rigid rotor/harmonic oscillator/ideal gas approximation based on ab initio characteristics and evaluation of relative populations from the molecular dynamic simulations using the AMBER potential) and both yield four structures, the global minimum and three local minima. These four structures were among the 15 most energetically stable structures obtained from accurate ab initio optimization. The calculated IR spectra for these four structures agree well with the experimental frequencies, which validates the localization procedure.

Gases↗
PubMed2005

Hydration-induced changes of structure and vibrational frequencies of methylphosphocholine studied as a model of biomembrane lipids.

The chemical characteristics of the polar parts of phospholipids as the main components of biological membranes were investigated by using infrared (IR) spectroscopy and theoretical calculations with water as a probe molecule. The logical key molecule used in this study is methylphosphocholine (MePC) as it is not only a representative model for a polar lipid headgroup but itself has biological significance. Isolated MePC forms a compact (folded) structure which is essentially stabilized by two intramolecular C-H...O type hydrogen bonds. At lower hydration, considerable wavenumber shifts were revealed by IR spectroscopy: the frequencies of the (O-P-O)- stretches were strongly redshifted, whereas methyl and methylene C-H and O-P-O stretches shifted surprisingly to blue. The origin of both red- and blueshifts was rationalized, on the basis of molecular-dynamics and quantum-chemistry calculations. In more detail, the hydration-induced blueshifts of C-H stretches could be shown to arise from several origins: disruption of the intramolecular C-H...O hydrogen bonds, formation of intermolecular C-H...O(water) H-bonds. The stepwise disruption of the intramolecular hydrogen bonds appeared to be the main feature that causes partial unfolding of the compact structure. However, the transition from a folded to extended MePC structure was completed only at high hydration. One might hypothesize that the mechanism of hydration-driven conformational changes as described here for MePC could be transferred to other zwitterions with relevant internal C-H...O hydrogen bonds.

Computer Simulation↗
PubMed2001

The nature of improper, blue-shifting hydrogen bonding verified experimentally.

In the infrared spectra of solutions in liquid argon of dimethyl ether ((CH(3))(2)O) and fluoroform (HCF(3)), bands due to a 1:1 complex between these monomers have been observed. The C-H stretch of the HCF(3) moiety in the complex appears 17.7 cm(-1) above that in the monomer, and its intensity decreases by a factor of 11(2). These characteristics situate the interaction between the monomers in the realm of improper, blue-shifting hydrogen bonding. The complexation shifts the C-F stretches downward by some 9 cm(-1), while the C-H stretches in (CH(3))(2)O are shifted upward by 9-15 cm(-1), and the C-O stretches are shifted downward by 5 cm(-1). These shifts are in very good agreement with those calculated by means of correlated ab initio methods, and this validates a two-step mechanism for improper, blue-shifting hydrogen bonding. In the first step, the electron density is transferred from the oxygen lone electron pairs of the proton acceptor ((CH(3))(2)O) to fluorine lone electron pairs of the proton donor (CHF(3)) which yields elongation of all CF bonds. Elongation of CF bonds is followed (in the second step) by structural reorganization of the CHF(3) moiety, which leads to the contraction of the CH bond. It is thus clearly demonstrated that not only the spectral manifestation of H-bonding and improper H-bonding but also their nature differ.

Chlorofluorocarbons, Methane↗
PubMed2001

At nonzero temperatures, stacked structures of methylated nucleic acid base pairs and microhydrated nonmethylated nucleic acid base pairs are favored over planar hydrogen-bonded structures: a molecular dynamics simulations study.

The dynamic structure of all ten possible nucleic acid (NA) base pairs and methylated NA base pairs hydrated by a small number of water molecules (from 1 to 16) was determined by using molecular dynamics simulations in the NVE microcanonical and NVT canonical ensembles with the Cornell force field (W. D. Cornell, P. Cieplak, C. I. Bayly, I. R. Gould, K. M. Merz, D. M. Ferguson, D. C. Spellmeyer, T. Fox, J. E. Caldwell, P. Kollman, J. Am. Chem. Soc. 1995, 117, 5179). The presence of one water molecule does not affect the structure of any hydrogen-bonded (H-bonded) nonmethylated base pair. An equal population of H-bonded and stacked structures of adenine...adenine, adenine...guanine and adenine... thymine pairs is reached if as few as two water molecules are present, while obtaining equal populations of these structures in the case of adenine...cytosine, cytosine...thymine, guanine... guanine and guanine...thymine required the presence of four water molecules, and in the case of guanine...cytosine, six. A comparable population of planar, H-bonded and stacked structures for cytosine...cytosine and thymine... thymine base pairs was only obtained if at least eight water molecules hydrated a pair. Methylation of bases changed the situation dramatically and stacked structures were favoured over H-bonded ones even in the absence of water molecules in most cases. Only in the case of methyl cytosine...methyl cytosine, methyl guanine...methyl guanine and methyl guanine...methyl cytosine pairs were two, two or six water molecules, respectively, needed in order to obtain a comparable population of planar, H-bonded and stacked structures. We believe that these results give clear evidence that the preferred stacked structure of NA base pairs in the microhydrated environment, and also apparently in a regular solvent, is due to the hydrophilic interaction of a small number of water molecules. In the case of methylated bases, it is also due to the fact that the hydrogen atoms most suitable for the formation of H-bonds have been replaced by a methyl group. A preferred stacked structure is, thus, not due to a hydrophobic interaction between a large bulk of water molecules and the base pair, as believed.

Base Pairing↗
PubMed2000

Sequence-dependent elastic properties of DNA.

Harmonic elastic constants of 3-11 bp duplex DNA fragments were evaluated using four 5 ns unrestrained molecular dynamics simulation trajectories of 17 bp duplexes with explicit inclusion of solvent and counterions. All simulations were carried out with the Cornell et al. force-field and particle mesh Ewald method for long-range electrostatic interactions. The elastic constants including anisotropic bending and all coupling terms were derived by analyzing the correlations of fluctuations of structural properties along the trajectories. The following sequences have been considered: homopolymer d(ApA)(n) and d(GpG)(n), and alternating d(GPC)(n) and d(APT)(n). The calculated values of elastic constants are in very good overall agreement with experimental values for random sequences. The atomic-resolution molecular dynamics approach, however, reveals a pronounced sequence-dependence of the stretching and torsional rigidity of DNA, while sequence-dependence of the bending rigidity is smaller for the sequences considered. The earlier predicted twist-bend coupling emerged as the most important cross-term for fragments shorter than one helical turn. The calculated hydrodynamic relaxation times suggest that damping of bending motions may play a role in molecular dynamics simulations of long DNA fragments. A comparison of elasticity calculations using global and local helicoidal analyses is reported. The calculations reveal the importance of the fragment length definition. The present work shows that large-scale molecular dynamics simulations represent a unique source of data to study various aspects of DNA elasticity including its sequence-dependence.

Algorithms↗
PubMed2000

Structure, energetics, vibrational frequencies and charge transfer of base pairs, nucleoside pairs, nucleotide pairs and B-DNA pairs of trinucleotides: ab initio HF/MINI-1 and empirical force field study.

Geometries, interaction energies and vibrational frequencies of base pairs, nucleoside pairs and nucleotide pairs were studied by ab initio Hartree-Fock (HF) method using MINI-1 basis set and empirical Cornell et al. force field (AMBER 4.1). A good agreement was found between HF/MINI-1 and AMBER results. In addition, both methods provide reasonable agreement with available high-level ab initio data. Finally, AMBER potential was used to determine the structure, energetics and vibrational frequencies of B-DNA pairs of trinucleotides. Stabilization energies of clusters are lowered when passing from base pairs to nucleoside pairs, nucleotide pairs and to pairs of trinucleotides. The lowest vibrations of base pairs and nucleoside pairs correspond to intermolecular motions of bases, specifically to buckle and propeller motions. In the case of pairs of larger subunits the lowest vibrations are of intramolecular nature (rotation around glycosidic bond, sugar and phosphate vibration). The spectra of these clusters became more complicated and quasi-degenerate. Intermolecular charge transfer between bases in H-bonded and stacked pairs is negligible, while a significant intramolecular charge transfer was observed.

Base Pairing↗
PubMed1999

Metal ions in non-complementary DNA base pairs: an ab initio study of Cu(I), Ag(I), and Au(I) complexes with the cytosine-adenine base pair.

Ab initio calculations have been carried out to characterize the structure and energetics of a silver(I) complex with the cytosine-adenine DNA base pair and an aqua ligand in the coordination sphere of Ag. In addition, we have also studied analogous complexes with Cu(I) and Au(I), and structures in which adenine has been replaced by purine in order to investigate the structural role of the adenine amino group. The calculations revealed that all metal-modified structures are dominated by the metal-base interactions, while the water-metal ion interaction and many-body interligand repulsion are less important contributions. Nevertheless, the structural role of the water molecule in the complex is quite apparent and in agreement with an earlier crystallographic study. The metal-modified base pairs exhibit large conformational flexibility toward out-of-plane motions (propeller twist and buckle), comparable or, in some cases, even larger than that observed in the base pairs without metal ions. All structures have been optimized within the Hartree-Fock approximation, while interaction energies were evaluated with the inclusion of electron correlation.

Adenine↗
PubMed1999

Interactions of hydrated IIa and IIb group metal cations with thioguanine-cytosine DNA base pair: Ab initio and density functional theory investigation of polarization effects, differences among cations, and flexibility of the cation hydration shell.

The structures and energies of the thioguanine-cytosine Watson-Crick (thioGC WC) base pair interacting with hydrated IIa (Mg2+, Ca2+, Ba2+) and IIb group (Zn2+, Cd2+, Hg2+) cations have been studied using ab initio techniques. Furthermore, complexes between guanine and thioguanine with hydrated cations have been characterized assuming various structures of the hydration shells. The complexes of the thioGC WC base pair with hydrated cations have similar properties as the previously studied GC WC base pair. There is substantial polarization stabilization of the base pairing due to cation binding which amounts to 7 - 11 kcal/mol. Soft Cd2+ and Hg2+ cations have a uniquely strong interaction with the thiogroup and induce substantial nonplanarity of the pairing. The thiogroup tends to reduce the number of water molecules in the first hydration shell of the cation. All complexes were optimized within the Hartree-Fock (HF) approximation while their energetics has been evaluated using the second-order Moller-Plesset perturbational method (MP2). All interaction energy evaluations and a substantial portion of the optimizations of the hydrated cation-(thio)guanine complexes have been repeated using Becke-3LYP Density Functional Theory method. All three approximations used (HF, Becke-3LYP, and MP2) give qualitatively the same results for the present cationic complexes. The results demonstrate specific differences among the cations and provide a set of reference structures and energies for verification and/or parametrization of empirical potentials and other theoretical methods.

Barium↗
PubMed1997

Base-base and deoxyribose-base stacking interactions in B-DNA and Z-DNA: a quantum-chemical study.

Base-stacking interactions in canonical and crystal B-DNA and in Z-DNA steps are studied using the ab initio quantum-chemical method with inclusion of electron correlation. The stacking energies in canonical B-DNA base-pair steps vary from -9.5 kcal/mol (GG) to -13.2 kcal/mol (GC). The many-body nonadditivity term, although rather small in absolute value, influences the sequence dependence of stacking energy. The base-stacking energies calculated for CGC and a hypothetical TAT sequence in Z-configuration are similar to those in B-DNA. Comparison with older quantum-chemical studies shows that they do not provide even a qualitatively correct description of base stacking. We also evaluate the base-(deoxy)ribose stacking geometry that occurs in Z-DNA and in nucleotides linked by 2',5'-phosphodiester bonds. Although the molecular orbital analysis does not rule out the charge-transfer n-pi* interaction of the sugar 04' with the aromatic base, the base-sugar contact is stabilized by dispersion energy similar to that of stacked bases. The stabilization amounts to almost 4 kcal/mol and is thus comparable to that afforded by normal base-base stacking. This enhancement of the total stacking interaction could contribute to the propensity of short d(CG)n sequences to adopt the Z-conformation.

Base Composition↗
PubMed1997

Hydrogen-bonded trimers of DNA bases and their interaction with metal cations: ab initio quantum-chemical and empirical potential study.

Neutral (G.GC, A.AT, G.AT, T.AT, and C(imino).GC) and protonated (CH+.GC and AH+.GC) hydrogen-bonded trimers of nucleic acid bases were characterized by ab initio methods with the inclusion of electron correlation. In addition, the influence of metal cations on the third-strand binding in Purine-Purine-Pyrimidine (Pu.PuPy) reverse-Hoogsteen triplets has been studied. The ab initio calculations were compared with those from recently introduced force fields (AMBER4.1, CHARMM23, and CFF95). The three-body term in neutral trimers is mostly negligible, and the use of empirical potentials is justified. The only exception is the neutral G.GC Hoogsteen trimer with a three-body term of -4 kcal/mol. Protonated trimers are stabilized by molecular ion-molecular dipole attraction and the interaction within the complex is nonadditive, with the three-body term on the order of -3 kcal/mol. There is a significant induction interaction between the third-strand protonated base and guanine. The calculations indicate an enhancement of the third-strand binding in the G.GC reverse-Hoogsteen trimer due to-metal cation coordination to the N7/O6 position of the third-strand guanine. Interactions between metal cations and complexes of DNA bases are in general highly non-additive; the three-body term is above-10 kcal/mol in a complex of a divalent cation (Ca2+) with the GG reverse-Hoogsteen pair. The pairwise additive empirical potentials qualitatively underestimate the binding energy between cation and base.

Adenine↗
PubMed1996

Base stacking and hydrogen bonding in protonated cytosine dimer: the role of molecular ion-dipole and induction interactions.

An ab initio quantum-chemical study of stacked and hydrogen-bonded protonated cytosine dimer has been carried out. The calculations were made using the second-order Moller-Plesset perturbational method (MP2) with a medium-sized polarized set of atomic orbitals. H-bonded as well as stacked protonated base pairs are more stable than the neutral base pairs. Two energy contributions not present in the neutral base pairs stabilize the protonated base pairs: the molecular ion - dipole interaction, and the induction interaction. The molecular ion - dipole stabilization dominates in base pairs with highly polar neutral monomers, such as the C...CH+ base pair. The induction interaction is not included in the commonly used empirical potentials, which do not reproduce the changes in intermolecular stabilization due to protonation. We demonstrate that the base stacking of several consecutive C...CH + pairs, as proposed for polycytidylic acid and i-DNA, is strongly repulsive. We also show that the intermolecular interactions strongly prefer protonation of adenine in protonated adenine-cytosine pairs.

Base Composition↗
PubMed1996

Nonplanar DNA base pairs.

Three-dimensional structures of a representative set of more than 30 hydrogen-bonded nucleic acids pairs have been studied by reliable ab initio quantum mechanical methods. We show that many hydrogen-bonded nucleic acid base pairs are intrinsically nonplanar, mainly due to the partial sp3 hybridization of nitrogen atoms of their amino groups and secondary electrostatic interactions. This finding extends the variability of intermolecular interactions of DNA bases in that i) flexibility of the base pairs is larger than has been assumed before, and ii) attractive proton-proton acceptor interactions oriented out of the base pair plane are allowed. For example, all four G-A mismatch base pairs are propeller twisted, and the energy preferences for the nonplanar structures range from less than 0.1 kcal/mol to 1.8 kcal/mol. We predict that nonplanarity of the amino group of guanine in the G(anti)...A(anti) pair of the ApG step of the d(CCAAGATTGG)2 crystal structure is an important stabilizing factor that improves the energy of this structure by almost 3 kcal/mol. Currently used empirical potentials are not accurate enough to properly cover the interactions associated with amino-group and base-pair nonplanarity.

Base Composition↗
PubMed1996

Hydrogen bonding and stacking of DNA bases: a review of quantum-chemical ab initio studies.

Ab initio quantum-chemical calulations with inclusion of electron correlation made since 1994 (such reliable calculations were not feasible before) significantly modified our view on interactions of nucleic acid bases. These calculations allowed to perform the first reliable comparison of the strength of stacked and hydrogen bonded pairs of nucleic acid bases, and to characterize the nature of the base-base interactions. Although hydrogen-bonded complexes of nucleobases are primarily stabilized by the electrostatic interaction, the dispersion attraction is also important. The stacked pairs are stabilized by dispersion attraction, however, the mutual orientation of stacked bases is determined rather by the electrostatic energy. Some popular theories of stacking were ruled out: The theory based on attractive interactions of polar exocyclic groups of bases with delocalized electrons of the aromatic rings (Bugg et al., Biopolymers 10, 175 (1971), and the pi-pi interactions model (C.A. Hunter, J. Mol. Biol. 230, 1025 (1993)). The calculations demonstrated that amino groups of nucleobases are very flexible and intrinsically nonplanar, allowing hydrogen-bond-like interactions which are oriented out of the plane of the nucleobase. Many H-bonded DNA base pairs are intrinsically nonplanar. Higher-level ab initio calculations provide a unique set of reliable and consistent data for parametrization and verification of empirical potentials. In this article, we present a short survey of the recent calculations, and discuss their significance and limitations. This summary is written for readers which are not experts in computational quantum chemistry.

Base Composition↗
PubMed1994

An empirical potential study of the interaction of L-lysine-L-alanine-L-alanine tripeptide with four models of B-DNA with different compositions.

The empirical potential including the intra- and intermolecular energy terms was used to study the interaction of L-Lysine-L-Alanine-L-Alanine Tripeptide with four models of B-DNA with different compositions. On the basis of a detailed search of the respective potential energy surface, it was found that the peptide is preferentially bounded to the AT-rich sequences. Analysis of the different energy contributions indicated that the electrostatic term is responsible for this preference. The results agree with the experimental data on the selectivity of some DNA--binding proteins and polypeptides to AT-rich DNA.

Base Sequence↗