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Modulation of protein-protein interactions by competitive small-molecule binding emerges as a promising avenue for drug discovery. Hot spots, i.e., amino acids with important contributions to the overall interaction energy, provide useful targets within these interfaces. To avoid time-consuming mutagenesis experiments, computational alanine screening has been developed for the prediction of hot spots based on existing structural information. Here we use the all-atom free-energy force field PFF02 to identify important amino acid residues in the complexes of the chemokine interleukin-8 (CXCL8) and an N-terminal peptide of its cognate receptor CXCR1, and of ERBIN, a molecular marker of the basolateral membrane in epithelial cells, in complex with the ERBIN-binding domain of tyrosin kinase ERBB2. The results of our analysis agree with available experimental functional assays, indicating that this approach is suitable for computational alanine screening and may help to identify competitive peptides as starting points for the development of inhibitors of protein-protein interactions for pharmaceutically relevant targets.

We compare two procedures to gain efficiency by approximating two-electron integrals in molecular electronic structure calculations. The first one is based on a Cholesky decomposition (CD) of two-electron integrals, the second one on the use of preoptimized auxiliary or fitting basis sets employed in a "resolution of the identity" (RI) technique. We present and test auxiliary bases for approximating the Coulomb term, which further improves accuracy over previously proposed fitting bases. It is shown that RI methods lead to insignificant errors only, which are partly comparable to or even better than that of CD treatments; but RI procedures are superior in speed. CD methods have certain advantages, however, particularly for extended basis sets.

For the reliable long-term modeling of the actinide migration in geological formations, the adsorption/desorption properties and the reactivity of mineral surfaces must be understood at the molecular level. The adsorption of radioisotopes at mineral surfaces of the aquifer is an important process that leads to the retention of contaminants such as radionuclides. Their transport by the ground water is either retarded or even completely inhibited by the presence of such a surface. Accordingly, this subject is of main importance for the safety assessment of nuclear waste repositories. As part of a joint theoretical/experimental effort, the interaction of water with the corundum (0001) surface is studied using several theoretical methods (Moller-Plesset perturbation theory, coupled cluster singles doubles with triplet corrections, as well as density functional theory). We focus in this study on the determination of the bond lengths and tilt angles of the surface OH species and their respective vibrational frequencies. The theoretical results are confirmed by subsequent simulation of the interface selective nonlinear sum frequency spectra. The excellent agreement of the simulated with the experimental spectra allows an assignment of the observed peaks in the sum frequency spectra of the water/corundum (0001) interface on the basis of our theoretical data. In this theoretical study we are able to give a unique interpretation of the observed sum frequency spectra of the water/corundum (0001) interface.

With the atomistic Kubo-Verges method we calculate the ballistic conductance of various conformers of DNA (A,B,Z), as well as intermediate and composite conformations, using experimental structures and model complexes. For duplexes with 6 and 15 base pairs, we find that the valence band conductivity near the Fermi edge varies dramatically between the different conformations, most notably for the B-to-Z transition. The latter conductivity differences are largely unchanged both in the presence and in the absence of trimethylthiol linkers between DNA and gold electrodes in vacuo, but become much less drastic when explicit molecular dynamics and water-counterion surrounding of B- and Z-DNA are taken into account. Based on atomistic structural models, we argue that changes in the electrostatic energy in the presence of an applied external electric field can induce conformational switching that may be exploited in novel DNA-based memory devices of high packing density.

Electron detachment from fullerene dianions Cm2- (m=76,84) stored in a room temperature Penning trap was probed upon pulsed laser excitation at wavelengths of 355 and 532 nm. The fraction of Cm(2-) surviving trapping times exceeding tens of milliseconds under UHV conditions, as well as the fraction of singly charged anions Cm(-) generated were recorded as a function of the laser fluence. Analysis by means of Poisson statistics yields absolute absorption cross sections and the number of photons necessary to induce the detachment. The cross sections obtained are in good agreement with the literature values. By describing the electron detachment as a statistical unimolecular process, we deduce effective activation energies from the number of photons required. These energies are compared to the sum of the second electron affinity and the Coulomb barrier height as calculated from an electrostatic charging model.

Small beta hairpins have many distinct biological functions, including their involvement in chemokine and viral receptor recognition. The relevance of structural similarities between different hairpin loops with near homologous sequences is not yet understood, calling for the development of methods for de novo hairpin structure prediction and simulation. De novo folding of beta strands is more difficult than that of helical proteins because of nonlocal hydrogen bonding patterns that connect amino acids that are distant in the amino acid sequence and there is a large variety of possible hydrogen bond patterns. Here we use a greedy version of the basin hopping technique with our free-energy forcefield PFF02 to reproducibly and predictively fold the hairpin structure of a HIV-V3 loop. We performed 20 independent basin hopping runs for 500 cycles corresponding to 7.4 x 10(7) energy evaluations each. The lowest energy structure found in the simulation has a backbone root mean square deviation (bRMSD) of only 2.04 A to the native conformation. The lowest 9 out of the 20 simulations converged to conformations deviating less than 2.5 A bRMSD from native.

Response theory up to infinite order is combined with the explicitly correlated coupled-cluster singles and doubles model including linear-r(12) corrections, CCSD(R12). The additional terms introduced by the linear-r(12) contributions, not present in the conventional CCSD calculation, are derived and discussed with respect to the extra costs required for their evaluation. An implementation is presented up to the cubic response function for one-electron perturbations, i.e., up to frequency-dependent second hyperpolarizabilities. As first applications the authors computed the electronic polarizabilities and second hyperpolarizabilities of BH, N(2), and formaldehyde and show that the improvement in the one-electron basis set convergence known from the R12 method for ground state energies is retained for higher-order optical properties. Frequency-dependent results are presented for the second hyperpolarizability of N(2).

Near thermal energy reactive collisions of small mixed metal cluster cations Ag(m)Au(n) (+) (m+n=4, 5, and 6) with carbon monoxide have been studied in the room temperature Penning trap of a Fourier transform ion-cyclotron-resonance mass spectrometer as a function of cluster size and composition. The tetrameric species AgAu(3) (+) and Ag(2)Au(2) (+) are found to react dissociatively by way of Au or Ag atom loss, respectively, to form the cluster carbonyl AgAu(2)CO(+). In contrast, measurements on a selection of pentamers and hexamers show that CO is added with absolute rate constants that decrease with increasing silver content. Experimentally determined absolute rate constants for CO adsorption were analyzed using the radiative association kinetics model to obtain cluster cation-CO binding energies ranging from 0.77 to 1.09 eV. High-level ab initio density functional theory (DFT) computations identifying the lowest-energy cluster isomers and the respective CO adsorption energies are in good agreement with the experimental findings clearly showing that CO binds in a "head-on" fashion to a gold atom in the mixed clusters. DFT exploration of reaction pathways in the case of Ag(2)Au(2) (+) suggests that exoergicities are high enough to access the minimum energy products for all reactive clusters probed.

As known since about two decades, R12 methods, which include terms linear in the interelectronic distance r(12) in the wave function, improve substantially the basis set convergence of the ground state correlation energy. In a previous study, however, it was found that the same approach does not give a similar systematic improvement if applied to excited states in the framework of coupled cluster response theory. In the present work, we examine the reason for this behavior and show that the inclusion of additional orbitals in the construction of the r(12) pair functions leads to an enhanced basis set convergence (and thus a balanced description) also for the excited states.

The structures of mass selected silver cluster cations Ag19 +, Ag38 +, Ag55 +, Ag59 +, Ag75 +, and Ag79 + have been probed at a temperature of 100 K by trapped ion electron diffraction. The structure assignment is carried out by comparison of the experimental scattering intensity with theoretical scattering functions of calculated candidate structures obtained by density functional theory. For the cluster sizes studied the resulting experimental data are invariably best described by structures based on the icosahedral motif, while closed packed structures can be ruled out.

The microwave spectrum of m-cresol (3-methylphenol) has been investigated using a molecular beam Fourier transform microwave spectrometer in the frequency range from 3 to 26.5 GHz. The rotation of the hydroxy group into two different unequal energetic minima leads to different spectra for the syn- and anticonformers. Because of a high potential barrier both conformers can be analyzed independently. The methyl group is undergoing an almost free internal rotation which is only hindered by small barriers and splits the vibrational ground state in two states of internal rotation denoted as A and E species. The spacing between the species is found to be up to 10 GHz. The potential for the internal rotation can be determined from the spectra and analyzed in terms of the Fourier components V3 and V6. For syn-m-cresol these parameters were determined as V3=673(3) GHz and V6=-335(24) GHz and for anti-m-cresol V3=95(5) GHz and V6=-416(46) GHz. The barriers to internal rotation were furthermore calculated with second-order Moller-Plesset perturbation theory and second-order coupled-cluster singles- and-doubles model (CC2) in the electronic ground state and with CC2 in the first excited state. The CC2 method is found to be an appropriate method to calculate potential barriers in electronic excited states of such compounds.

We investigate different protocols of the basin hopping technique for de novo protein folding. Using the protein free-energy force field PFF01 we report the reproducible all-atom folding of the 20-amino-acid tryptophan-cage protein [Protein Data Bank (PDB) code: 112y] and of the recently discovered 26-amino-acid potassium channel blocker (PDB code: 1wqc), which exhibits an unusual fold. We find that simulations with increasing cycle length and random starting temperatures perform best in comparison with other parametrizations. The basin hopping technique emerges as a simple but very efficient and robust workhorse for all-atom protein folding.

Electron transfer collisions of trapped doubly charged fullerene anions C76(2-), C(78)2-, and C84(2-) with SF6 are studied in a Fourier transform ion cyclotron resonance mass spectrometer at center-of-mass collisional energies ranging from thermal energy to 77 eV. Collision energy dependencies manifest threshold energies for (nominally exoergic) single electron transfer onto SF6 of 1.46+/-0.3 eV, 1.56+/-0.3 eV, and 1.63+/-0.3 eV for C(76)2-, C78(2-), and C(84)2-, respectively. Kinetics studies reveal charge-transfer cross sections of up to 430+/-200 A2 for C84(2-) at a collision energy of 77 eV. The mechanism and the energetics are discussed in terms of classical electrostatic model calculations. Additionally, we rationalize the collision energy dependencies of the charge-transfer cross sections using the two-state Landau-Zener formalism to describe the associated resonant electron tunneling probability.

We evaluate the efficiency of multiple variants of energy landscape paving in all-atom simulations of the trp-cage protein using a recently developed new force field. Especially, we introduce a temperature-free variant of the method and demonstrate that it allows a fast scanning of the energy landscape. Nativelike structures are found in less time than by other techniques. The sampled low-energy configurations indicate a funnel-like energy landscape.

The Au-.CO2 ion-molecule complex has been studied by gas phase infrared photodissociation spectroscopy. Several sharp transitions can be identified as combination bands involving the asymmetric stretch vibrational mode of the CO2 ligand. Their frequencies are redshifted by several hundred cm(-1) from the frequencies of free CO2. We discuss our findings in the framework of ab initio and density-functional theory calculations, using anharmonic corrections to predict vibrational transition energies. The infrared spectrum is consistent with the formation of an aurylcarboxylate anion with a strongly bent CO2 subunit.

Room temperature CO adsorption on isolated gold cluster cations is studied over a wide size range (Au(n) (+),126), with notable exceptions at n=30, 31 and 48, 49 which manifest local binding energy maxima. For the smallest sizes (3

We report on the progress of our implementation of the configuration-selecting multireference configuration interaction method on massively parallel architectures with distributed memory, which now permits the treatment of Hilbert spaces of dimension O(10(12)). Of these about 50,000,000 can be selected in the variational subspace. We provide scaling data for the running time of the code for the IBM/SP3 and the CRAY-T3E. We present benchmark results for two selected applications: the energetics of the isomers of dinitrosoethylene and the benchmark results for the ring closure reaction of enediyene., (2005 American Institute of Physics.)

An approach to describe heteroatomic clusters A(n)B(N-n) as perturbed homoatomic ones is presented. By first treating the homoatomic systems A(N) or/and B(N) and subsequent application of first-order perturbation theory it is possible to estimate relative stabilities of the 2(N) possible distributions of the atom types A and B at the N atomic sites in a very efficient manner. The approach was tested considering Ir(n)Pt(13-n) as an example (treated with density functional methods). One observes good correlation between relative stabilities estimated from the homoatomic cases and those obtained from explicit treatments of the binary systems. Moreover we rationalize the observed correlation of atom type and atom position in Ir(n)Pt(13-n)., ((c) 2004 American Institute of Physics.)

Absorption spectra were measured for Ti2 in Ne and Ar matrices. The spectra give evidence for several electronic transitions in the region between 4000 and 10 000 cm(-1) and provide important information about some excited electronic states of Ti2 in proximity to the ground state. The vibrational fine structure measured for these transitions allowed to calculate the force constants and the anharmonicity of the potential energy curves of the excited states, and to estimate changes in the internuclear Ti-Ti distances relative to the electronic ground state. The quantum chemical studies confirm the previously suggested (3)Delta(g) state as the ground state of Ti2. The equilibrium bond distance is calculated to be 195.4 pm. The calculated harmonic frequency of 432 cm(-1) is in good agreement with the experimental value of 407.0 cm(-1). With the aid of the calculations it was possible to assign the experimentally observed transitions in the region between 4000 and 10 000 cm(-1) to the 1 (3)Pi(u)<--(3)Delta(g), 1 (3)Phi(u)<--(3)Delta(g), 2 (3)Pi(u)<--(3)Delta(g), 2 (3)Phi(u)<--(3)Delta(g), and (3)Delta(u)<--(3)Delta(g) excitations (in the order of increasing energy). The calculated relative energies and harmonic frequencies are in pleasing agreement with the experimentally obtained values, with deviations of less than 5% and 2%, respectively. The bond distances estimated on the basis of the experimental spectra tally satisfactorily with the predictions of our calculations.