Showing papers by "Pavel Hobza published in 2008"

Investigations into the Nature of Halogen Bonding Including Symmetry Adapted Perturbation Theory Analyses.

Abstract: In recent years it has been recognized that, because of their unique properties, halogen bonds have tremendous potential in the development of new pharmaceutical compounds and materials. In this study we investigate the phenomenon of halogen bonding by carrying out ab initio calculations on the halomethane-formaldehyde complexes as well as the fluorine substituted FnH3-nCX···OCH2 dimers, where the halogen bonding halogens (X) are chlorine, bromine, and iodine. Coupled cluster (CCSD(T)/aug-cc-pVTZ) calculations indicate that the binding energies for these type of interactions lie in the range between −1.05 kcal/mol (H3CCl···OCH2) and −3.72 kcal/mol (F3CI···OCH2). One of the most important findings in this study is that, according to symmetry adapted perturbation theory (SAPT) analyses, halogen bonds are largely dependent on both electrostatic and dispersion type interactions. As the halogen atom involved in halogen bonding becomes larger the interaction strength for this type of interaction also gets large...

Nature and magnitude of aromatic stacking of nucleic acid bases

Abstract: This review summarises recent advances in quantum chemical calculations of base-stacking forces in nucleic acids. We explain in detail the very complex relationship between the gas-phase base-stacking energies, as revealed by quantum chemical (QM) calculations, and the highly variable roles of these interactions in nucleic acids. This issue is rarely discussed in quantum chemical and physical chemistry literature. We further extensively discuss methods that are available for base-stacking studies, complexity of comparison of stacking calculations with gas phase experiments, balance of forces in stacked complexes of nucleic acid bases, and the relation between QM and force field descriptions. We also review all recent calculations on base-stacking systems, including details analysis of the B-DNA stacking. Specific attention is paid to the highest accuracy QM calculations, to the decomposition of the interactions, and development of dispersion-balanced DFT methods. Future prospects of computational studies of base stacking are discussed.

Benzene Dimer: High-Level Wave Function and Density Functional Theory Calculations.

Abstract: High-level OVOS (optimized virtual orbital space) CCSD(T) interaction energy calculations (up to the aug-cc-pVQZ basis set) and various extrapolations toward the complete basis set (CBS) limit are presented for the most important structures on the benzene dimer potential energy surface. The geometries of these structures were obtained via an all-coordinate gradient geometry optimization using the DFT-D/BLYP method, covering the empirical dispersion correction fitted exclusively for this system. The fit was carried out against two estimated CCSD(T)/CBS potential energy curves corresponding to the distance variation between two benzene rings for the parallel-displaced (PD) and T-shaped (T) structures. The effect of the connected quadruple excitations on the interaction energy was estimated using the CCSD(TQf) method in a 6-31G*(0.25) basis set, destabilizing the T and T-shaped tilted (TT) structures by ≈0.02 kcal/mol and the PD structure by ≈0.04 kcal/mol. Our best CCSD(T)/CBS results show, within the error bars of the applied methodology, that the energetically lowest-lying structure is the TT structure, which is nearly 0.1 kcal/mol more stable than the almost isoenergetic PD and T structures. The specifically parametrized DFT-D/BLYP method leads to a correct energy ordering of the structures, with the errors being smaller by 0.2 kcal/mol with respect to the most accurate CCSD(T) values.

Blue shifts vs red shifts in σ-hole bonding

Abstract: σ-Hole bonding is a noncovalent interaction between a region of positive electrostatic potential on the outer surface of a Group V, VI, or VII covalently-bonded atom (a σ-hole) and a region of negative potential on another molecule, e.g., a lone pair of a Lewis base. We have investigated computationally the occurrence of increased vibration frequencies (blue shifts) and bond shortening vs decreased frequencies (red shifts) and bond lengthening for the covalent bonds to the atoms having the σ-holes (the σ-hole donors). Both are possible, depending upon the properties of the donor and the acceptor. Our results are consistent with models that were developed earlier by Hermansson and by Qian and Krimm in relation to blue vs red shifting in hydrogen bond formation. These models invoke the derivatives of the permanent and the induced dipole moments of the donor molecule.

Benchmark database on isolated small peptides containing an aromatic side chain: comparison between wave function and density functional theory methods and empirical force field.

Abstract: A detailed quantum chemical study on five peptides (WG, WGG, FGG, GGF and GFA) containing the residues phenylalanyl (F), glycyl (G), tryptophyl (W) and alanyl (A)—where F and W are of aromatic character—is presented. When investigating isolated small peptides, the dispersion interaction is the dominant attractive force in the peptide backbone–aromatic side chain intramolecular interaction. Consequently, an accurate theoretical study of these systems requires the use of a methodology covering properly the London dispersion forces. For this reason we have assessed the performance of the MP2, SCS-MP2, MP3, TPSS-D, PBE-D, M06-2X, BH&H, TPSS, B3LYP, tight-binding DFT-D methods and ff99 empirical force field compared to CCSD(T)/complete basis set (CBS) limit benchmark data. All the DFT techniques with a ‘-D’ symbol have been augmented by empirical dispersion energy while the M06-2X functional was parameterized to cover the London dispersion energy. For the systems here studied we have concluded that the use of the ff99 force field is not recommended mainly due to problems concerning the assignment of reliable atomic charges. Tight-binding DFT-D is efficient as a screening tool providing reliable geometries. Among the DFT functionals, the M06-2X and TPSS-D show the best performance what is explained by the fact that both procedures cover the dispersion energy. The B3LYP and TPSS functionals—not covering this energy—fail systematically. Both, electronic energies and geometries obtained by means of the wave-function theory methods compare satisfactorily with the CCSD(T)/CBS benchmark data.

Quantum Chemical Benchmark Energy and Geometry Database for Molecular Clusters and Complex Molecular Systems (www.begdb.com): A Users Manual and Examples

Abstract: Our previous benchmark CCSD(T)/ complete basis set limit calculations were collected into a database named begdb - Benchmark Energy and Geometry DataBase. Web-based interface to this database was prepared and is available at www.begdb.com. Users can browse, search and plot the data online or download structures and energy tables.

Highly Accurate CCSD(T) and DFT–SAPT Stabilization Energies of H‐Bonded and Stacked Structures of the Uracil Dimer

Abstract: The CCSD(T) interaction energies for the H-bonded and stacked structures of the uracil dimer are determined at the aug-cc-pVDZ and aug-cc-pVTZ levels. On the basis of these calculations we can construct the CCSD(T) interaction energies at the complete basis set (CBS) limit. The most accurate energies, based either on direct extrapolation of the CCSD(T) correlation energies obtained with the aug-cc-pVDZ and aug-cc-pVTZ basis sets or on the sum of extrapolated MP2 interaction energies (from aug-cc-pVTZ and aug-cc-pVQZ basis sets) and extrapolated ΔCCSD(T) correction terms [difference between CCSD(T) and MP2 interaction energies] differ only slightly, which demonstrates the reliability and robustness of both techniques. The latter values, which represent new standards for the H-bonding and stacking structures of the uracil dimer, differ from the previously published data for the S22 set by a small amount. This suggests that interaction energies of the S22 set are generated with chemical accuracy. The most accurate CCSD(T)/CBS interaction energies are compared with interaction energies obtained from various computational procedures, namely the SCS–MP2 (SCS: spin-component-scaled), SCS(MI)–MP2 (MI: molecular interaction), MP3, dispersion-augmented DFT (DFT–D), M06–2X, and DFT–SAPT (SAPT: symmetry-adapted perturbation theory) methods. Among these techniques, the best results are obtained with the SCS(MI)–MP2 method. Remarkably good bindingmore » energies are also obtained with the DFT–SAPT method. Both DFT techniques tested yield similarly good interaction energies. The large magnitude of the stacking energy for the uracil dimer, compared to that of the benzene dimer, is explained by attractive electrostatic interactions present in the stacked uracil dimer. These interactions force both subsystems to approach each other and the dispersion energy benefits from a shorter intersystem separation.« less

Origin of the X-Hal (Hal = Cl, Br) bond-length change in the halogen-bonded complexes.

Abstract: The origin of the X-Hal bond-length change in the halogen bond of the X-Hal...Y type has been investigated at the MP2(full)/6-311++G(d,p) level of theory using a natural bond orbital analysis, atoms in molecules procedure, and electrostatic potential fitting methods. Our results have clearly shown that various theories explaining the nature of the hydrogen bond cannot be applied to explain the origin of the X-Hal bond-length change in the halogen bond. We provide a new explanation for this change. The elongation of the X-Hal bond length is caused by the electron-density transfer to the X-Hal sigma* antibonding orbital. For the blue-shifting halogen bond, the electron-density transfer to the X-Hal sigma* antibonding orbital is only of minor importance; it is the electrostatic attractive interaction that causes the X-Hal bond contraction.

Double-Helical → Ladder Structural Transition in the B-DNA is Induced by a Loss of Dispersion Energy

Abstract: The role of the dispersion energy and electrostatic energy on the geometry and stability of the B-DNA helix was investigated. Both molecular dynamics simulations with empirical force field and hybrid quantum mechanical/molecular mechanics molecular dynamics simulations, where the dispersion or electrostatics term is suppressed/increased, on the one hand and an ab initio minimization procedure on the other have shown that the lack of the dispersion term leads to an increase of the vertical separation of the bases as well as to a loss of helicity, thus resulting in a ladder-like structure. A decrease of the electrostatic term produces a separation of the DNA strands. The biological consequences of both electrostatic and dispersion forces in DNA are enormous, and without either of them, DNA would become unstable and unable to provide the storage and transfer of genetic information.

Another role of proline: stabilization interactions in proteins and protein complexes concerning proline and tryptophane

Abstract: Proline-tryptophan complexes derived from experimental structures are investigated by quantum chemical procedures known to properly describe the London dispersion energy. We study two geometrical arrangements: the "L-shaped", stabilized by an H-bond, and the "stacked-like", where the two residues are in parallel orientation without any H-bond. Interestingly, the interaction energies in both cases are comparable and very large ( approximately 7 kcal mol(-1)). The strength of stabilization in the stacked arrangement is rather surprising considering the fact that only one partner has an aromatic character. The interaction energy decomposition using the SAPT method further demonstrates the very important role of dispersion energy in such arrangement. To elucidate the structural features responsible for this unexpectedly large stabilization we examined the role of the nitrogen heteroatom and the importance of the cyclicity of the proline residue. We show that the electrostatic interaction due to the presence of the dipole, caused by the nitrogen heteroatom, contributes largely to the strength of the interaction. Nevertheless, the cyclic arrangement of proline, which allows for the largest amount of dispersive contact with the aromatic partner, also has a notable-effect. Geometry optimizations carried out for the "stacked-like" complexes show that the arrangements derived from protein structure are close to their gas phase optimum geometry, suggesting that the environment has only a minor effect on the geometry of the interaction. We conclude that the strength of proline non-covalent interactions, combined with this residue's rigidity, might be the explanation for its prominent role in protein stabilization and recognition processes.

Evaluation of the intramolecular basis set superposition error in the calculations of larger molecules: [n]helicenes and Phe-Gly-Phe tripeptide.

Abstract: Correlated ab initio calculations on large systems, such as the popular MP2 (or RI-MP2) method, suffer from the intramolecular basis set superposition error (BSSE). This error is typically manifested in molecules with folded structures, characterized by intramolecular dispersion interactions. It can dramatically affect the energy differences between various conformers as well as intramolecular stabilities, and it can even impair the accuracy of the predictions of the equilibrium molecular structures. In this study, we will present two extreme cases of intramolecular BSSE, the internal stability of [n]helicene molecules and the relative energies of various conformers of phenylalanyl-glycyl-phenylalanine tripeptide (Phe-Gly-Phe), and compare the calculated data with benchmark values (experimental or high-level theoretical data). As a practical and cheap solution to the accurate treatment of the systems with large anticipated value of intramolecular BSSE, the recently developed density functional method augmented with an empirical dispersion term (DFT-D) is proposed and shown to provide very good results in both of the above described representative cases.

Theoretical study on the complexes of benzene with isoelectronic nitrogen-containing heterocycles.

Abstract: The π–π interactions between benzene and the aromatic nitrogen heterocycles pyridine, pyrimidine, 1,3,5-triazine, 1,2,3-triazine, 1,2,4,5-tetrazine, and 1,2,3,4,5-pentazine are systematically investigated. The T-shaped structures of all complexes studied exhibit a contraction of the C—H bond accompanied by a rather large blue shift (40–52 cm−1) of its stretching frequency, and they are almost isoenergetic with the corresponding displaced-parallel structures at reliable levels of theory. With increasing number of nitrogen atoms in the heterocycle, the geometries, frequencies, energies, percentage of s character at C, and the electron density in the C—H σ antibonding orbital of the complexes all increase or decrease systematically. Decomposition analysis of the total binding energy showed that for all the complexes, the dispersion energy is the dominant attractive contribution, and a rather large attraction originating from electrostatic contribution is compensated by its exchange counterpart.

Potential-energy and free-energy surfaces of glycyl-phenylalanyl-alanine (GFA) tripeptide: experiment and theory.

Abstract: The free-energy surface (FES) of glycyl-phenylalanyl-alanine (GFA) tripeptide was explored by molecular dynamics (MD) simulations in combination with high-level correlated ab initio quantum chemical calculations and metadynamics. Both the MD and metadynamics employed the tight-binding DFT-D method instead of the AMBER force field, which yielded inaccurate results. We classified the minima localised in the FESs as follows: a) the backbone-conformational arrangement; and b) the existence of a COOH...OC intramolecular H-bond (families CO 2 H free and CO 2 H bonded ). Comparison with experimental results showed that the most stable minima in the FES correspond to the experimentally observed structures. Remarkably, however, we did not observe experimentally the CO 2 H bonded family (also predicted by metadynamics), although its stability is comparable to that of the CO 2 H free structures. This fact was explained by the former's short excited-state lifetime. We also carried out ab initio calculations using DFT-D and the M06-2X functional. The importance of the dispersion energy in stabilising peptide conformers is well reflected by our pioneer analysis using the DFT-SAPT method to explore the nature of the backbone/side-chain interactions.

The amino group in adenine: MP2 and CCSD(T) complete basis set limit calculations of the planarization barrier and DFT/B3LYP study of the anharmonic frequencies of adenine.

Abstract: The amino group in adenine plays a key role in formation of hydrogen bonds in nucleic acids and in other molecular systems. Thus, the structure of this group is of fundamental importance in the molecular recognition phenomena. Ab initio MP2 and density functional B3LYP methods with various basis sets have been used to calculate the optimized structure and the infrared spectrum of adenine (the N9-H tautomer). Calculations at the MP2 level with larger basis sets tend to decrease the degree of pyramidalization of the C-NH2 group, whereas the B3LYP method consistently yields the planar or nearly planar structure of adenine. MP2 complete basis set (CBS) limit method with the aug-cc-pVTZ --> aug-cc-pVQZ (aTZ --> aQZ) extrapolation scheme has predicted very small planarization barrier of adenine, 0.015 kcal/mol, which is in very good agreement with the MP2-predicted planarization barrier of 0.020 kcal/mol, reported by S. Wang and H. F. Schaefer III, J. Chem. Phys. 2006, 124, 044303. Similar results were obtained in calculations by the coupled cluster CCSD(T) CBS method. Thus, it can be concluded that the amino group in adenine, in the gas phase, is very flexible with a small degree of nonplanarity. Extremely low planarization barrier implies that adenine requires very little energy to conform the structure of the amino group to formation of the complementary hydrogen bonds with other molecules. This fact is very important for base pairing in nucleic acids or other polymers containing adenine residues. The anharmonic frequencies of adenine have been calculated at the B3LYP/6-311++G(df,pd) level of theory. The theoretical results show excellent agreement with the available experimental data. The revised assignment of the infrared spectrum of adenine in Ar matrix has been made. The predicted anharmonic frequency of the NH2 inversion, 181 cm(-1), is supported by the experimental data. It is demonstrated that the vibrational frequencies and potential energy distribution (PED) obtained from the B3LYP calculations are more reliable than those obtained at the MP2 level.

Interpretation of protein/ligand crystal structure using QM/MM calculations: case of HIV-1 protease/metallacarborane complex.

Abstract: Deltahedral metallacarborane compounds have recently been discovered as potent, specific, stable, and nontoxic inhibitors of HIV-1 protease (PR), the major target for AIDS therapy. The 2.15 A-resolution X-ray structure has exhibited a nonsymmetrical binding of the parental compound [Co3+-(C2B9H11)2]− (GB-18) into PR dimer and a symmetrical arrangement in the crystal of two PR dimer complexes into a tetramer. In order to explore structural and energetic details of the inhibitor binding, quantum mechanics coupled with molecular mechanics approach was utilized. Realizing the close positioning of anionic inhibitors in the active site cavity, the possibility of an exchange of structural water molecules Wat50 and Wat128 by Na+ counterions was studied. The energy profiles for the rotation of the GB-18 molecules along their longitudinal axes in complex with PR were calculated. The results show that two Na+ counterions are present in the active site cavity and provide energetically favorable and unfavorable positi...

Non-standard base pairing and stacked structures in methyl xanthine clusters

Abstract: We present resonant two-photon ionization and IR–UV double resonance spectra of methylated xanthine derivatives including 7-methylxanthine dimer and theobromine dimer seeded in a supersonic jet by laser desorption. For 7-methylxanthine, theophylline and theobromine monomer we assign the lowest energy tautomer based on comparison with IR–UV double resonance spectra and calculated IR frequencies. For the 7-methylxanthine dimer, we observe hydrogen bonding on the N3H position suggesting 3 possible combinations, one that is reverse Watson–Crick type and two that are reverse Hoogsteen type. For the theobromine dimer, we observe a stacked structure. For trimethylxanthine dimers we infer a stacked structure as well.

Benzene Dimer: Dynamic Structure and Thermodynamics Derived from On-the-Fly ab initio DFT-D Molecular Dynamic Simulations

Abstract: The dynamic nature of the benzene dimer was explored by on-the-fly molecular dynamics simulations based on the DFT-D method covering the dispersion energy. An all-electron DFT was performed at the BLYP/TZVP level. The parameters in the dispersion correction term were fitted to mimic the benchmark CCSD(T)/complete basis set limit potential energy curves for both the parallel-displaced (PD) and T-shaped (TS) structures of the dimer exactly. A dynamic description is important at temperatures above 10 K, where interconversion between the TS and PD structures is possible and a mixture of these two species exists. The higher the temperature, the more dominant the TS structure because of a favorable entropic contribution to the free energy. An analysis of the TS structures revealed that the symmetric c2v structure, a low-lying transition state, is practically not populated and that the tilted cs TS structure is prevalent. This finding is in perfect agreement with infrared spectroscopy.

Adsorption of aromatic hydrocarbons and ozone at environmental aqueous surfaces.

Abstract: Adsorption of environmentally important aromatic molecules on a water surface is studied by means of classical and ab initio molecular dynamics simulations and by reflection−absorption infrared spectroscopy. Both techniques show strong activity and orientational preference of these molecules at the surface. Benzene and naphthalene, which bind weakly to water surface with a significant contribution of dispersion interactions, prefer to lie flat on water but retain a large degree of orientational flexibility. Pyridine is more rigid at the surface. It is tilted with the nitrogen end having strong hydrogen bonding interactions with water molecules. The degree of adsorption and orientation of aromatic molecules on aqueous droplets has atmospheric implications for heterogeneous ozonolysis, for which the Langmuir−Hinshelwood kinetics mechanism is discussed. At higher coverages of aromatic molecules the incoming ozone almost does not come into contact with the underlying aqueous phase. This may rationalize the ex...

Electronic splitting in the excited states of DNA base homodimers and -trimers: an evaluation of short-range and Coulombic interactions.

Abstract: The nature of the electronic interactions of the stacked nucleic-acid bases (adenine, thymine, cytosine, and uracil) in homodimer and -trimer complexes in their electronically excited states was investigated and analysed in terms of orbital-overlap and Coulombic interactions. The mutual orientations of the adjacent bases were selected so as to correspond to the A- and B-DNA conformations. The extent of the electronic interaction is larger for the former conformation. It is shown that the orbital-overlap interactions at the distance of two bases relevant to the DNA structure do not contribute significantly to the overall electronic coupling. Only the states which are caused by the (π → π*) transitions manifest an electronic coupling.

Identifying stabilizing key residues in proteins using interresidue interaction energy matrix.

Abstract: We are proposing an interresidue interaction energy map (IEM)--a new tool for protein structure analysis and protein bioinformatics. This approach employs the sum of pair-wise interaction energies of a particular residue as a measure of its structural importance. We will show that the IEM can serve as a means for identifying key residues responsible for the stability of a protein. Our method can be compared with the interresidue contact map but has the advantage of weighting the contacts by the stabilization energy content which they bring to the protein structure. For the theoretical adjustment of the proposed method, we chose the Trp-cage mini protein as a model system to compare a spectrum of computational methods ranging from the ab initio MP2 level through the DFT method to empirical force-field methods. The IEM method correctly identifies Tryptophane 6 as the key residue in the Trp-cage. The other residues with the highest stabilizing contributions correspond to the structurally important positions in the protein. We have further tested our method on the Trp2Cage miniprotein--a P12W mutant of the Trp-cage and on two proteins from the rubredoxin family that differ in their thermostability. Our method correctly identified the thermodynamically more stable variants in both cases and therefore can also be used as a tool for the relative measurement of protein stability. Finally, we will point out the important role played by dispersion energy, which contributes significantly to the total stabilization energy and whose role in aromatic pairs is clearly dominant. Surprisingly, the dispersion energy plays an even more important role in the interaction of prolines with aromatic systems.

State of the art theoretical study and comparison to experiment for the phenol...argon complex.

Abstract: The phenol center dot center dot center dot argon complex was studied by means of various high level ab initio quantum mechanics methods and high resolution threshold ionization spectroscopy. The structure and stabilization energy of different conformers were determined. Stabilization energy of van der Waals bonded and H-bonded PhOH center dot center dot center dot Ar complex determined at CCSD(T) complete basis set (CBS) level for CP-RI-MP2/cc-pVTZ/Ar aug-cc-pVTZ geometries amount to 434 and 285 cm(-1). The CCSD(T)/CBS were constructed either as a sum of MP2/CBS interaction energy and CCSD(T) correction term [difference between CCSD(T) and MP2 correlation energies determined with medium basis set] or directly from CCSD(T)/aug-cc-pVDZ and aug-cc-pVTZ energies. Both schemes provide very similar values. Harmonic vibrational analysis revealed that the H-bonded structure does not represent energy minimum but first order transition structure. The respective imaginary vibrational mode (16 cm(-1)) connects two possible argon locations-above and below the phenol aromatic ring. Including the Delta ZPVE, we obtained stabilization enthalpy at 0 K of 389 cm(-1). This value is marginally higher (25-35 cm(-1), 0.07-0.10 kcal/mol) than the experimental value. The determination of Delta ZPVE constitutes the most significant error and possible improvements should come from more accurate evaluation of the (nonharmonic) vibrational frequencies. (c) 2008 American Institute of Physics.

On the importance of electron correlation effects for the intramolecular stacking geometry of a bis-thiophene derivative.

Abstract: The structure of dithienobicyclo[4.4.1]undeca-3,8-diene-11-one ethylene glycol ketal (database code RESVAN) was determined using the wave function theory (WFT) as well as density functional theory (DFT) methods combined with various Gaussian AO basis sets. The apparently most accurate procedure, employing the CCSD(T)/complete basis set (CBS), provides an S-S distance and an angle between the two thiophene rings which differ considerably from experimental values. The best agreement with the experimental data among all WFT methods was surprisingly obtained at the MP3/aug-cc-pVDZ and MP3/CBS(B) levels (the correction term to CBS was obtained by the aug-cc-pVDZ basis set). The very good results obtained by the CCSD(T)/ 6-31G* method are clearly a consequence of fortunate error compensation. MP2 calculations, even with a small basis set, overestimate the attraction between the thiophene rings, and the worst agreement with experimental data was found in full MP2/QZVP method optimizations (i.e., a strong distortion of the thiophene rings was observed). The SCS(MI)-MP2 and SCS-MP2 methods exhibit improvement over the MP2 procedure. All standard DFT approaches fail to predict reasonable S-S distances. The lack of intramolecular London dispersion energy results in too great distance between the thiophene rings. Much better agreement with experiment was obtained if advanced DFT methods, covering dispersion effects, were used. The best results were obtained at the TPSS-D/TZVP, M06-L/TZVP and B2PLYP-D/def2-TZVP levels. When a larger basis (LP in the case of TPSS functional) or more advanced versions of the new Truhlar functionals (M06-2X) was used, the agreement with experiment deteriorated. The accurate description of this molecule is highly functional/ basis dependent and this dependence is hardly predictable. To estimate effects of neighboring molecules in the experimental crystal structure, an optimization in the electric field of the 26 closest RESVAN molecules was performed, which, however, leads to only moderate (<0.05 A) changes of the S-S distance.

A DFT-D investigation of the mechanisms for activation of the wild-type and S810L mutated mineralocorticoid receptor by steroid hormones.

Abstract: In this work, we investigate the mode of binding of several steroid hormones, namely aldosterone, deoxycorticosterone, and progesterone to the wild-type and S810L mutated mineralocorticoid (MR) receptor using the newly formulated density functional theory with an empirical dispersion term (DFT-D) molecular electronic structure method. It is found that the MR agonists, aldosterone and deoxycorticosterone, form tight hydrogen bonds with residues Thr945 and Asn770, which leads to the formation of hydrogen bond networks near the steroid D-ring, allowing for activation of this transcription factor. Progesterone, an MR antagonist, fails to form the necessary hydrogen bonds near the steroid D-ring. Progesterone is known to be an agonist of the mutated S810L MR receptor. Our studies indicate that this is possible because of a strong hydrogen bond between progesterone and Thr945 and a relatively strong hydrophobic interaction between progesterone and Asn770.

Application of Berlin's Theorem to Bond-Length Changes in Isolated Molecules and Red- and Blue-Shifting H-Bonded Clusters

Abstract: The origin of the bond-length change in molecule or molecular cluster has been investigated at the MP2/aug-cc-pVDZ level of theory using the electrostatic potential or the electron density difference analysis method. Our results have clearly shown that the bond-length change of a chemical bond is determined mainly by the balance of the electrostatic forces exerted by electrons on the two nuclei. The factors that affect the balance of the electrostatic forces include four parts: (i) The abstraction of the electron density from Berlin's binding region between the two nuclei. (ii) The accumulation of the electron density in Berlin's antibinding regions. (iii) The accumulation of the electron density in Berlin's binding region between the two nuclei. (iv) The abstraction of the electron density from Berlin's antibinding regions. Using the change of the electron density around the two nuclei of a chemical bond, we have succeeded in explaining two important chemical phenomena: (i) breakdown of bond length-bond strength correlation; (ii) the bond-length change in the hydrogen bond.

Assigning the NH stretches of the guanine tautomers using adiabatic separation: CCSD(T) benchmark calculations.

Abstract: Using an adiabatic separation of the NH stretching vibration from the remaining vibrational molecular motions, the NH fundamental frequencies and absolute intensities of several keto/enol and 7/9NH tautomers of guanine are evaluated ab initio within the framework of a one-dimensional "semirigid" stretching Hamiltonian. The frequencies (calculated by means of the standard MP2, CCSD(T) and DFT procedures) are in a close one-to-one harmony with their experimental counterparts, thus evidencing the adequacy of the used separation for reliable assigning of the NH stretches in the vibrational spectra of very large molecular systems.

The Stabilization Energy of the GLU-LYS Salt Bridge in the Protein/Water Environment: Correlated Quantum Chemical ab initio , DFT and Empirical Potential Studies

Abstract: The stabilization energies of Glu-Lys salt bridges are calculated at the CCSD(T) complete basis set limit to provide a reasonable description of the strength of the ion-pair bond in the gas phase. The effect of the environment (protein with e = 4 and water with e = 80) on the stabilization energy was introduced via a modification of the quantum chemical DFT energy, for which the COSMO methodology was adopted. The other (standard) approach was based on incorporating a dielectric constant into the Coulomb electrostatic term of the Amber empirical potential function and utilizing the generalized Born model implemented in the Amber program. The environment affects the stabilization energy of the salt bridge dramatically: The protein reduces the energy to less than one half of the original value, whereas water sometimes changes stabilization to destabilization. Both theoretical procedures, based on completely different theoretical backgrounds, yield very similar results, which strongly support their validity. An ion pair is converted to an ion-neutral pair when its pH is changed. This transformation is connected with a strong reduction of the stabilization energy regardless of the environment. The substantial differences in the stabilization energies of ion pairs and ion-neutral pairs contradict the negligible changes of free energy detected experimentally. Evidently, the contribution of formation and hydration entropy is significant and compensates for the large stabilization energies.

Correlation Between the Thermodynamic Stability of DNA Duplexes and the Interaction and Solvation Energies of DNA Building Blocks

Abstract: The unwinding Gibbs energy (or duplex dissociation energy) is an important measure of the thermodynamic stability of DNA oligomers. This value can be measured experimentally or predicted by empirical models parametrised on experimental data. Our previously developed model based on accurate DFT-D calculations of interaction energies between nucleic acid bases corrected for solvation contribution. This work was successfully extended to cover variable lengths of oligomers. This model was further applied to oligomers containing inosine, an unnatural base. The results, however, are not satisfactory and it is clear that the model does not take into account all variables contributing to DNA stability. Inclusion of the backbone deformation energy did not improve the model. We also compared models based on DFT-D and forcefield calculations. Forcefield performs well in this application, because the systematic error in interaction energies is cancelled in the fitting procedure.