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A state-averaged, multireference complete active space (CAS) approach was used for the determination of the vertical excitation energies of valence and Rydberg states of para-benzyne. Orbitals were generated with a 10- and 32-state averaged multiconfigurational self-consistent field approach. Electron correlation was included using multireference configuration interaction with singles and doubles, including the Pople correction for size extensivity, multireference averaged quadratic coupled cluster (MR-AQCC), and MR-AQCC based on linear response theory. There is a very high density of electronic states in this diradical system—there are more than 17 states within 7 eV of the ground state including two 3s Rydberg states. All excitations, except 2 1Ag, are from the π system to the σσ* system. Of the 32 states characterized, 15 were multiconfigurational, including the ground 1Ag state, providing further evidence for the necessity of a multireference approach for p-benzyne. The vertical singlet-triplet splitting was also characterized using a two-state averaged approach. A CAS(2,2) calculation was shown to be inadequate due to interaction with the π orbitals. [ABSTRACT FROM AUTHOR]

The base pairing of 9-deaza-2' -deoxyguanosine (CdG) is examined by incorporating it into DNA and paired it with either dC or dA. The results have shown that CdG:dC base pairs are destabilized relative to dG:dC as a result of structural constraints imposed by the C-nucleotide character of CdG and CdG:dA base pairs are less stable than OdG:dA base pairs because of a third long-range interaction that is possible in OdG:dA but not in CdG:dA.

The Low Mode:Monte Carlo (LM:MC) conformational search method is used for examining the low energy structures for (3R,4aS,7aR,11aS,12aR)-11a-methyl-3-phenyldecahydro-1H-[1,3]dioxino[5,4-b]pyrano[2,3-g]oxocine, a model for the FHG rings in brevetoxin A, a potent marine toxin. The lowest energy structure has depended on the force field-solvent treatment and the twist-crown and boat-chair conformers are lowest in energy.

Large basis set ab initio calculations have been carried out for a dense grid of points on the He3 potential energy surface. Three-body contributions were extracted at every point, and a number of concise functional representations for the three-body potential surface were then examined. Three-body multipolar dispersion terms and other radial and angular terms were used in the representations, and an assessment of relative importance of the different terms is presented. Combined with a two-body He–He potential, the results of this work should offer a high quality interaction potential for simulations of aggregated helium. [ABSTRACT FROM AUTHOR]

High level ab initio calculations have been carried out to assess the pairwise additivity of potentials in the attractive or well regions of the potential surfaces of clusters of helium atoms. A large basis set was employed and calculations were done at the Brueckner orbital coupled cluster level. Differences between calculated potentials for several interacting atoms and the corresponding summed pair potentials reveal the three-body and certain higher order contributions to the interaction strengths. Attraction between rare gas atoms develops from dispersion, and so helium clusters provide the most workable systems for analyzing nonadditivity of dispersion. The results indicate that the many-body or nonpairwise contributions tend to be less than a few percent of the attractive interaction across regions around the minima of the potential energy surfaces of small clusters. Dipole–dipole–dipole dispersion and dipole–dipole–quadrupole dispersion are noticeable parts of the small three-body terms. [ABSTRACT FROM AUTHOR]

ABSTRACT Mutations in the amyloid precursor protein (APP) are responsible for the formation of amyloid-β peptides. These peptides play a role in Alzheimer's and other dementia-related diseases. The cargo binding domain of the kinesin-1 light chain motor protein (KLC1) may be responsible for transporting APP either directly or via interaction with C-jun N-terminal kinase-interacting protein 1 (JIP1). However, to date there has been no direct experimental or computational assessment of such binding at the atomistic level. We used molecular dynamics and free energy estimations to gauge the affinity for the binary complexes of KLC1, APP, and JIP1. We find that all binary complexes (KLC1:APP, KLC1:JIP1, and APP:JIP1) contain conformations with favorable binding free energies. For KLC1:APP the inclusion of approximate entropies reduces the favorability. This is likely due to the flexibility of the 42-residue APP protein. In all cases we analyze atomistic/residue driving forces for favorable interactions. Proteins 2017; 85:221-234. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

During DNA replication, DNA polymerases follow an induced fit mechanism in order to rapidly distinguish between correct and incorrect dNTP substrates. The dynamics of this process are crucial to the overall effectiveness of catalysis. Although X-ray crystal structures of DNA polymerase I with substrate dNTPs have revealed key structural states along the catalytic pathway, solution fluorescence studies indicate that those key states are populated in the absence of substrate. Herein, we report the first atomistic simulations showing the conformational changes between the closed, open, and ajar conformations of DNA polymerase I in the binary (enzyme∶DNA) state to better understand its dynamics. We have applied long time-scale, unbiased molecular dynamics to investigate the opening process of the fingers domain in the absence of substrate for B. stearothermophilis DNA polymerase in silico. These simulations are biologically and/or physiologically relevant as they shed light on the transitions between states in this important enzyme. All closed and ajar simulations successfully transitioned into the fully open conformation, which is known to be the dominant binary enzyme-DNA conformation from solution and crystallographic studies. Furthermore, we have detailed the key stages in the opening process starting from the open and ajar crystal structures, including the observation of a previously unknown key intermediate structure. Four backbone dihedrals were identified as important during the opening process, and their movements provide insight into the recognition of dNTP substrate molecules by the polymerase binary state. In addition to revealing the opening mechanism, this study also demonstrates our ability to study biological events of DNA polymerase using current computational methods without biasing the dynamics. [ABSTRACT FROM AUTHOR]