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This work presents that Cu with atomic-scale spacings (ds) efficiently catalyses the electrochemical co-reduction of CO2 and NO3− to urea. Specifically, Cu with ds near 6 Å (6 Å-Cu) produces urea with a high yield rate and partial current density.

By controlling the temporal and spatial features of light, we propose a novel protocol to prepare two-qubit entangling gates on atoms trapped at close distance, which could potentially speed up the operation of the gate from the sub-micro to the nanosecond scale. The protocol is robust to variations in the pulse areas and the position of the atoms, by virtue of the coherent properties of a dark state, which is used to drive the population through Rydberg states. From the time-domain perspective, the protocol generalizes the one proposed by Jaksch and coworkers [Jaksch et al., Phys. Rev. Lett. 85, 2208 (2000)], with three pulses that operate symmetrically in time, but with different pulse areas. From the spatial-domain perspective, it uses structured light. We analyze the map of the gate fidelity, which forms rotated and distorted lattices in the solution space. Finally, we study the effect of an additional qubit to the gate performance and propose generalizations that operate with multi-pulse sequences., Comment: 9 pages, 7 figures

α-Synuclein is a presynaptic neuronal protein. The fibril form of α-synuclein is a major constituent of the intraneuronal inclusion called Lewy body, a characteristic hallmark of Parkinson’s disease. Recent ssNMR and cryo-EM experiments of wild-type α-synuclein fibrils have shown polymorphism and observed two major polymorphs, rod and twister. To associate the cytotoxicity of α-synuclein fibrils with their structural features, it is essential to understand the origins of their structural stability. In this study, we performed molecular dynamics simulations of the two major polymorphs of wild-type α-synuclein fibrils. The predominance of specific fibril polymorphs was rationalized in terms of relative structural stability in aqueous environments, which was attributed to the cooperative contributions of various stabilizing features. The results of the simulations indicated that highly stable structures in aqueous environments could be maintained by the cooperation of compact sidechain packing in the hydrophobic core, backbone geometry of the maximal β-sheet content wrapping the hydrophobic core, and solvent-exposed sidechains with large fluctuations maximizing the solvation entropy. The paired structure of the two protofilaments provides additional stability, especially at the interface region, by forming steric zipper interactions and hiding the hydrophobic residues from exposure to water. The sidechain interaction analyses and pulling simulations showed that the rod polymorph has stronger sidechain interactions and exhibits higher dissociation energy than the twister polymorph. It is expected that our study will provide a basis for understanding the pathogenic behaviors of diverse amyloid strains in terms of their structural properties. Communicated by Ramaswamy H. Sarma

Activation entropy (ΔS‡) is not normally considered the main factor in determining the reactivity of unimolecular reactions. Here, we report that the intramolecular degradation of six-membered ring compounds is mainly determined by the ΔS‡, which is strongly influenced by the ring-flipping motion and substituent geometry. Starting from the unique difference between the pH-dependent degradation kinetics of geometric isomers of 1,2-cyclohexanecarboxylic acid amide (1,2-CHCAA), where only the cis isomer can readily degrade under weakly acidic conditions (pH < 5.5), we found that the difference originated from the large difference in ΔS‡ of 16.02 cal·mol–1·K–1. While cis-1,2-CHCAA maintains a preference for the classical chair cyclohexane conformation, trans-1,2-CHCAA shows dynamic interconversion between the chair and twisted boat conformations, which was supported by both MD simulations and VT-NMR analysis. Steric repulsion between the bulky 1,2-substituents of the trans isomer is one of the main reasons for the reduced energy barrier between ring conformations that facilitates dynamic ring inversion motions. Consequently, the more dynamic trans isomer exhibits much a larger loss in entropy during the activation process due to the prepositioning of the reactant than the cis isomer, and the pH-dependent degradation of the trans isomer is effectively suppressed. When the ring inversion motion is inhibited by an additional methyl substituent on the cyclohexane ring, the pH degradability can be dramatically enhanced for even the trans isomer. This study shows a unique example in which spatial arrangement and dynamic properties can strongly influence molecular reactivity in unimolecular reactions, and it will be helpful for the future design of a reactive structure depending on dynamic conformational changes.

We found that electron attachment to the van der Waals complex (O2···CO2) turns the weak intermolecular bond into a pseudochemical bond of significant strength. The resulting monomeric molecular anion (O2-CO2)- may be a form of CO4-, the gaseous anionic species suspected to be present in Earth's ionosphere whose chemical characteristics have not been comprehensively identified since its existence was first predicted by Conway in 1962. The measured vertical detachment energy of CO4- is very large (4.56 ± 0.05 eV), while the known electron affinity of its component species is much smaller (0.448 eV, O2) or even negative (-0.6 eV, CO2). These characteristics are correctly borne out by theoretical calculations that show that electron attachment transforms the van der Waals complex to a single contiguous molecular anion, with the formation of a pseudochemical bond between O2 and CO2 through an extended π-orbital system.

We performed molecular dynamics simulations of self-assembled supramolecular nanotubules constructed from amphiphiles with bent-shaped rods. By systematically examining the structure from dimeric aggregates to the fully developed nanotubule, we identified the basic building block of the nanotubule and the optimal dimensions of its stable structure which are consistent with experimental findings. Moreover, we demonstrate that the cooperative interplay of different interactions drives aggregation by selecting and stabilizing the optimal self-assembled structures for various intermediates through a complex pathway. Additionally, contraction of the nanotubule, which accompanies the dehydration process, was observed upon heating. It is suggested that the optimal stability of the self-assembled aggregates is achieved by balancing entropic and enthalpic contributions, of which the ratio is a critical factor that drives the aggregation pathway.

We found that electron attachment to the van der Waals complex (O

The native structure of a protein is stabilized by a number of interactions such as main-chain hydrogen bonds and side-chain hydrophobic contacts. However, it has been challenging to determine how these interactions contribute to protein stability at single amino acid resolution. Here, we quantified site-specific thermodynamic stability at the molecular level to extend our understanding of the stabilizing forces in protein folding. We derived the free energy components of individual amino acid residues separately for the folding of the human Pin WW domain based on simulated structures. A further decomposition of the thermodynamic properties into contributions from backbone and side-chain groups enabled us to identify the critical residues in the secondary structure and hydrophobic core formation, without introducing physical modifications to the system as in site-directed mutagenesis methods. By relating the structural and thermodynamic changes upon folding for each residue, we find that the simultaneous formation of the backbone hydrogen bonds and side-chain contacts cooperatively stabilizes the folded structure. The identification of stabilizing interactions in a folding protein at atomic resolution will provide molecular insights into understanding the origin of the protein structure and into engineering a more stable protein.

Amyloid deposits of Aβ protein in neuronal cells are known to be a major symptom of Alzheimer’s disease. In particular, Aβ42 shows relatively high toxicity among the different Aβ isoforms, and its ...

While the neuropathological characteristics of Niemann-Pick disease type C (NPC) result in a fatal diagnosis, the development of clinically available therapeutic agent remains a challenge. Here we propose graphene quantum dots (GQDs) as a potential candidate for the impaired functions in NPC in vivo. In addition to the previous findings that GQDs exhibit negligible long-term toxicity and are capable of penetrating the blood-brain barrier, GQD treatment reduces the aggregation of cholesterol in the lysosome through expressed physical interactions. GQDs also promote autophagy and restore defective autophagic flux, which, in turn, decreases the atypical accumulation of autophagic vacuoles. More importantly, the injection of GQDs inhibits the loss of Purkinje cells in the cerebellum while also demonstrating reduced activation of microglia. The ability of GQDs to alleviate impaired functions in NPC proves the promise and potential of the use of GQDs toward resolving NPC and other related disorders.

In order to realize electrochemically efficient hydrogen production, various endeavors have been devoted to developing hydrogen evolution reaction (HER) electrocatalysts having zero hydrogen binding energy (ΔGH⁎ = 0) for balancing between adsorption and desorption. This work demonstrated that nitrogen doping improved the HER activity of ruthenium oxide by letting its ΔGH⁎ approach zero or facilitating hydrogen desorption process. A highly nitrogen-doped ruthenium oxide catalyst guaranteeing the ruthenium-nitrogen intimacy was prepared by employing a polymer whose nitrogen-containing moiety (pyrrolidone) was strongly coordinated to ruthenium ion in the precursor solution prior to calcination. The less electronegative nature of nitrogen (when compared with oxygen) decreased the free energy uphill required for desorption of hydrogen intermediate species sitting on the nitrogen (H-*N to 1/2 H2 + *N) to make the desorption process more favored. Also, the nitrogen dopant facilitated OH- desorption from its neighboring ruthenium site (HO-*Ru + e- to HO- + *Ru) since the less electronegative nitrogen withdrew less electrons from the ruthenium site. The ruthenium-nitrogen intimacy of the catalyst more than doubled the electrocatalytic HER current from 33 mA cm-2 for an undoped RuO2 to 79 mA cm-2 for the nitrogen-doped RuO2 at -50 mVRHE.

Mutations in the fasciclin 1 domain 4 (FAS1-4) of transforming growth factor β-induced protein (TGFBIp) are associated with insoluble extracellular deposits and corneal dystrophies (CDs). The decrease in solubility upon mutation has been implicated in CD; however, the exact molecular mechanisms are not well understood. Here, we performed molecular dynamics simulations followed by solvation thermodynamic analyses of the FAS1-4 domain and its three mutants-R555W, R555Q, and A546T-linked to granular corneal dystrophy type 1, Thiel-Behnke corneal dystrophy and lattice corneal dystrophy, respectively. We found that both R555W and R555Q mutants have less affinity toward solvent water relative to the wild-type protein. In the R555W mutant, a remarkable increase in solvation free energy was observed because of the structural changes near the mutation site. The mutation site W555 is buried in other hydrophobic residues, and R557 simultaneously forms salt bridges with E554 and D561. In the R555Q mutant, the increase in solvation free energy is caused by structural rearrangements far from the mutation site. R558 separately forms salt bridges with D575, E576, and E598. Thus, we thus identified the relationship between the decrease in solubility and conformational changes caused by mutations, which may be useful in designing potential therapeutics and in blocking FAS1 aggregation related to CD.

Synergistic effects of dual homogeneous catalysts for chemical reactions have been reported. Double activation (chemical transformation process where both catalysts work in concert to activate reactants or intermediates) was often responsible for the synergistic effects of dual catalyst systems. Herein, we demonstrate the extension of the double activation from chemo-catalysis to electrocatalysis. The activity of low-cost cobalt oxide electrocatalysts for oxygen reduction reaction (ORR) was significantly improved by introducing secondary-amine-conjugated polymers (HN-CPs) as the secondary promoting electrocatalyst (shortly, promoter). It was proposed that HN-CPs activated neutral diatomic oxygen to partially charged species (O2δ-) in the initial oxygen adsorption step of ORR. Electron donation number of HN-CP to diatomic oxygen (δ in O2δ-) well described the order of activity improvement, i.e., polypyrrole (pPy) > polyaniline (pAni) > polyindole (pInd). The maximum overpotential gain at ~150 mV was achieved by using pPy with the highest δ. Also, it was confirmed that proton of HN-CP was transferred to single oxygen intermediate (*O) of ORR.

We obtained the electronic spectra of various methylated xanthine compounds including caffeine in a supersonic jet by resonant two-photon ionization spectroscopy. The methyl group in the tested methylated xanthine compounds has a distinct, site-dependent effect on the electronic spectrum. Methylation at the N3 position causes a significant red shift of the ππ* state, whereas methylation at the N1 position has only minimal effects on the electronic spectrum. The notably broad spectra of theobromine and caffeine result from methyl substitution at the N7 position, which causes a large displacement between the potential energy surfaces of the S0 and S1 states, and a strong vibronic coupling. We also investigated the internal rotation of the methyl group and its effect on the electronic spectrum of the methylated xanthine compounds. We found that the barrier height for the torsional motion in the ground state is significantly affected by a carbonyl or methyl group that lies close to the methyl group of interest. In contrast, the torsional barrier in the excited state is governed by the hyperconjugation interaction in the lowest unoccupied molecular orbital. The agreement between the experimental and simulated spectra of torsional vibronic bands suggested that the low frequency torsional vibrations arising from the tunneling splitting and the coupling between the torsional and molecular motions give theobromine and theophylline the multiplet nature of their origin bands. This study provides a new level of understanding for the methyl substitution effects on the electronically excited states of xanthine compounds, which may very well be applicable to many other methyl substituted biomolecules including DNAs and proteins.

Although the replica exchange methods (REMs) were developed as efficient conformational sampling methods for bio-molecular simulations, their application to very large bio-systems is somewhat limited. We propose a new replica exchange scheme (Tq-REM) created by combining the conventional temperature-REM (T-REM) and one of the Hamiltonian-REMs, q-REM, using the effective potential with reduced barriers. In the proposed Tq-REM scheme, high temperature replicas in T-REM are substituted with q-replicas. This combined scheme is expected to exploit advantages of the T-REM and q-REM resulting in improved sampling efficiency while minimizing the drawbacks of both approaches. We investigated the performance of Tq-REM compared with T-REM by performing all-atom MD simulations on Met-enkephalin, (AAQAA)3, and Trpzip2. It was found that convergence of the free energy surfaces was improved by Tq-REM over the conventional T-REM. In particular, the trajectories of Tq-REM were able to sample the relevant conformations for all of the metastable folding intermediates, while some of the local minimum structures are poorly represented by T-REM. The results of the present study suggest that Tq-REM can provide useful tools to investigate systems where metastable states play important roles.

Amyloid deposits of Aβ protein in neuronal cells are known to be a major symptom of Alzheimer's disease. In particular, Aβ

The two-dimensional electron-nuclear Schr\"odinger equation using soft-core Coulomb potentials has been a cornerstone for modeling and predicting the behavior of one-active-electron diatomic molecules, particularly for processes where both bound and continuum states are important. The model, however, is computationally expensive to extend to more electron or nuclear coordinates. Here we propose to use the Ehrenfest approach to treat the nuclear motion, while the electronic motion is still solved by quantum propagation on a grid. In this work we present results for a one-dimensional treatment of H$_2^+$, where the quantum and semi-classical dynamics can be directly compared, showing remarkably good agreement for a variety of situations. The advantage of the Ehrenfest approach is that it can be easily extended to treat as many nuclear degrees of freedom as needed.

We predict anti-alignment dynamics in the excited state of H2+ or related homonuclear dimers in the presence of a strong field. This effect is a general indirect outcome of the strong transition dipole and large polarizabilities typically used to control or to induce alignment in the ground state. In the excited state, however, the polarizabilities have the opposite sign than in the ground state, generating a torque that aligns the molecule perpendicular to the field, deeming any laser-control strategy impossible., Comment: 4 figures

While the emerging evidence indicates that the pathogenesis of Parkinson's disease (PD) is strongly correlated to the accumulation of alpha-synuclein ({\alpha}-syn) aggregates, there has been no clinical success in anti-aggregation agents for the disease to date. Here we show that graphene quantum dots (GQDs) exhibit anti-amyloid activity via direct interaction with {\alpha}-syn. Employing biophysical, biochemical, and cell-based assays as well as molecular dynamics (MD) simulation, we find that GQDs have notable potency in not only inhibiting fibrillization of {\alpha}-syn but also disaggregating mature fibrils in a time-dependent manner. Remarkably, GQDs rescue neuronal death and synaptic loss, reduce Lewy body (LB)/Lewy neurite (LN) formation, ameliorate mitochondrial dysfunctions, and prevent neuron-to-neuron transmission of {\alpha}-syn pathology induced by {\alpha}-syn preformed fibrils (PFFs) in neurons. In addition, in vivo administration of GQDs protects against {\alpha}-syn PFFs-induced loss of dopamine neurons, LB/LN pathology, and behavioural deficits through the penetration of the blood-brain barrier (BBB). The finding that GQDs function as an anti-aggregation agent provides a promising novel therapeutic target for the treatment of PD and related {\alpha}-synucleinopathies.

We lay out the foundations of a general method of quantum control via geometrical optimization. We apply the method to state-selective population transfer using ultrashort transform-limited pulses between manifolds of levels that may represent, e.g., state-selective transitions in molecules. Assuming that certain states can be prepared, we develop three implementations: (i) preoptimization, which implies engineering the initial state within the ground manifold or electronic state before the pulse is applied; (ii) postoptimization, which implies engineering the final state within the excited manifold or target electronic state, after the pulse; and (iii) double-time optimization, which uses both types of time-ordered manipulations. We apply the schemes to two important dynamical problems: To prepare arbitrary vibrational superposition states on the target electronic state and to select weakly coupled vibrational states. Whereas full population inversion between the electronic states only requires control at initial time in all of the ground vibrational levels, only very specific superposition states can be prepared with high fidelity by either pre- or postoptimization mechanisms. Full state-selective population inversion requires manipulating the vibrational coherences in the ground electronic state before the optical pulse is applied and in the excited electronic state afterward, but not during all times.

Recently, a rational approach for constructing β-barrel protein mimics by the self-assembly of peptide-based building blocks has been demonstrated. We performed molecular dynamics simulations of nanoring formation by means of the self-assembly of designed β-sheet-forming peptides. Several factors contributing to the stability of the nanoring structures with respect to size were investigated. Our simulations predicted that an optimal nanoring size may be achieved by minimizing repulsions due to steric hindrance between bulky groups while maintaining favorable hydrogen-bond interactions between neighboring β-sheet chains. It was shown that mutations in a test peptide, in which all or half of the tryptophan residues were replaced by phenylalanine, could enable the assembly of stable nanoring structures with smaller pore sizes. Insights into the fundamental factors driving the formation of peptide-based nanostructures are expected to facilitate the design of novel functional bionanostructures.

The detailed mechanism of the pathology of α-synuclein in the Parkinson’s disease has not been clearly elucidated. Recent studies suggested a possible chaperone-like role of the acidic C-terminal region of α-synuclein in the formation of amyloid fibrils. It was also previously demonstrated that the α-synuclein amyloid fibril formation is accelerated by mutations of proline residues to alanine in the acidic region. We performed replica exchange molecular dynamics simulations of the acidic and nonamyloid component (NAC) domains of the wild type and proline-to-alanine mutants of α-synuclein under various conditions. Our results showed that structural changes induced by a change in pH or an introduction of mutations lead to a reduction in mutual contacts between the NAC and acidic regions. Our data suggest that the highly charged acidic region of α-synuclein may act as an intramolecular chaperone by protecting the hydrophobic domain from aggregation. Understanding the function of such chaperone-like parts of fibril-forming proteins may provide novel insights into the mechanism of amyloid formation.

Quantum systems with sublevel structures, like molecules, prevent full population inversion from one manifold of sublevels to the other using ultrafast resonant pulses. We explain the mechanism by which this population transfer is blocked. We then develop a novel concept of geometric control, assuming full or partial coherent manipulation within the manifolds, and show that by preparing specific coherent superpositions in the initial manifold, full population inversion or full population blockade, that is, laser transparency, can be achieved. By properly choosing the relative phases of the initial state, one can interfere in the stimulated emission process, changing the pattern of Rabi oscillations so that full population inversion to the excited electronic state can be achieved almost regardless of the pulse intensity after a minimal threshold value. This is the basis of a novel control mechanism, termed parallel transfer.

We study laser-driven isomerization reactions through an excited electronic state using the recently developed Geometrical Optimization procedure [J. Phys. Chem. Lett. 6, 1724 (2015)]. The goal is to analyze whether an initial wave packet in the ground state, with optimized amplitudes and phases, can be used to enhance the yield of the reaction at faster rates, exploring how the geometrical restrictions induced by the symmetry of the system impose limitations in the optimization procedure. As an example we model the isomerization in an oriented 2,2'-dimethyl biphenyl molecule with a simple quartic potential. Using long (picosecond) pulses we find that the isomerization can be achieved driven by a single pulse. The phase of the initial superposition state does not affect the yield. However, using short (femtosecond) pulses, one always needs a pair of pulses to force the reaction. High yields can only be obtained by optimizing both the initial state, and the wave packet prepared in the excited state, implying the well known pump-dump mechanism.

We show numerically that it is possible to control the bond distance of the RbCs dimer and create laser-induced oscillations using a single chirped pulse. The implementation of the scheme involves the creation of a superposition of the 1 3 Σ + and 2 3 Σ + excited triplet electronic states. We assume that the molecule is aligned and the dynamics is initiated in the bound 2 3 Σ + state. The chirped pulse allows full population transfer and dynamic vibrational trapping in the 1 3 Σ + state. In the adiabatic regime the position of the vibrational wave packet can be fully controlled by the carrier frequency of the field, so that one can determine and fix the bond length at any desired value, or impose particular trajectories, depending on the choice of the chirp.

We performed computational studies on the removal of an epoxide group from oxidized zigzag graphene nanoribbons (ZGNRs). Using density functional theory (DFT) calculations, we investigated the reaction mechanisms for the two competing processes, migration and reduction of an epoxide group in the middle of a narrow ZGNR. We found that the relative magnitudes of the barriers for migration and reduction depend on the width of the ZGNR. The reaction barrier for the reduction of an epoxide by CO decreased as the width of the ZGNR increased, while the barrier for migration showed the opposite trend. Moreover, the transition state energies for migration and reduction decreased upon the applied electric field perpendicular to the surface of the ZGNR. Our results illustrate that the removal of an epoxide from a ZGNR by reduction with CO can be facilitated by the application of an external electric field. For narrow ZGNRs, epoxide migration to neighboring sites may compete with the reduction reaction.

In this work we report control on the photoassociation of a proton and a Helium cation, or an alpha particle and an Hydrogen atom, to form HeH2+ assisted by strong femtosecond laser pulses. The results follow from the numerical solution of the time-dependent Schrodinger equation using soft-core Coulomb potentials in a ( 1 + 1 )D model (one dimension for the electronic motion plus one dimension for the nuclear motion) and for a nuclear Hamiltonian describing the dynamics in four electronic states. We study the dependence of the photoassociation yield on the initial nuclear wave function for a hot collision (impact kinetic energy of the order of a eV) and on the laser parameters. We predict high sensitivity on the synchronization of the laser with the collision time and Rabi oscillations for the yield as a function of the pulse amplitude and duration, while the ionization and inelastic scattering can be minimized with pulses of 50 fs or shorter.

E-mail: sshin@snu.ac.kr (S. Shin); sisid1@snu.ac.kr (C. Shin)Received October 25, 2013, Accepted December 11, 2013Time-dependent formulations of the reactive scattering theory based on the wavepacket correlation functionswith the Moller wavepackets for the electronically nonadiabatic reactions are presented. The calculations ofstate-to-state reactive probabilities for the quasi-Jahn-Teller scattering model system were performed. Theconical intersection (CI) effects are investigated by comparing the results of the two-surface nonadiabaticcalculations and the single surface adiabatic approximation. It was found that the results of the two-surfacenonadiabatic calculations show interesting features in the reaction probability due to the conical intersection.Single surface adiabatic calculations with extended Born-Oppenheimer approximation using simplewavepacket phase factor was found to be able to reproduce the CI effect semi-quantitatively, while the singlesurface calculations with the usual adiabatic approximation cannot describe the scattering process for the Jahn-Teller model correctly. Key Words : Wavepacket correlation function, Nonadiabatic reaction, Conical intersectionIntroduction Reactive scattering studies have been successful for 3-and 4-atom bimolecular reactions.

A hybrid modeling strategy using readily assigned Nuclear Overhauser Effect (NOE) data and main chain N–O contact information from homology template proteins is suggested. They are designed to be complementary. The strategy yields structures with reasonable root-mean square distance (RMSD) and NOE violation. When compared to homology-modeled structures, the hybrid-modeled structures are better in terms of RMSD, RMS NOE violation, and protein-like scores, although the number of used restraints is smaller than the homology modeling. The structure itself can be used as a theoretically modeled structure and also as a starting point for further NOE data assignment in structure determination.

The influence of pyridine adsorption and the applied electric field on the band structure and metallicity of zigzag graphene nanoribbons (ZGNRs) was investigated by using density functional theory (DFT) calculations. The semiconducting ZGNRs became half-metallic or remained semiconducting depending on the configuration of N–C covalent bonds between pyridine and the outermost C atom of the ZGNRs. In addition, the band gap of the α- and β-spin states of the ZGNRs could be tuned by noncovalent bonds. This effect was enhanced when BF3 was introduced simultaneously at the opposite edge. The applied external electric field also modulated the band structures of the ZGNRs, making them half-metallic or semiconducting to some extent. These features suggest that the well-arranged adsorption of pyridine and BF3 could be used to tune the band structures of nanoscale electronic devices based on graphene.

A homology model builder using simple restraining potentials based on spline-interpolated quadratic functions is developed and interfaced with CHARMM package. The continuity and stability of the potential function were validated, and the parameters were optimized using the CASP7 targets. The performance of the model builder was benchmarked to the Modeller program using the template-based modeling targets in CASP9. The benchmark results show that, while our builder yields the structures with slightly lower packing, backbone, and template modeling scores, our models show much better protein-like scores in terms of normalized discrete optimized protein energy, dipolar distance-scaled finite-ideal gas reference, Molprobity clash, Ramachandran appearance Z-score, and rotamer Z-score. As our model builder is interfaced with CHARMM, it is advantageous to directly use other CHARMM functionality and energy functions to refine the model structures or to use the models for other computational studies using CHARMM.

We have studied the oligomerization of a fibril-forming segment of -Synulcein using a replica exchange molecular dynamics (REMD) simulation. The simulation was performed with trimers and tetramers of a 12 amino acid residue stretch (residues 71-82) of -Synulcein. From extensive REMD simulations, we observed the spontaneous formation of both trimer and tetramer, demonstrating the self-aggregating and fibril-forming properties of the peptides. Secondary structure profile and clustering analysis illustrated that antiparallel -sheet structures are major species corresponding to the global free energy minimum. As the size of the oligomer increases from a dimer to a tetramer, conformational stability is increased. We examined the evolution of simple order parameters and their free energy profiles to identify the process of aggregation. It was found that the degree of aggregation increased as time passed. Tetramer formation was slower than trimer formation and a transition in order parameters was observed, indicating the full development of tetramer conformation which is more stable than that of the trimer. The shape of free energy surface and change of order parameter distributions indicate that the oligomer formation follows a dock-and-lock process.

Recently, control over the bond length of a diatomic molecule with the use of parabolic chirped pulses was predicted on the basis of numerical calculations [Chang; et al. Phys. Rev. A 2010, 82, 063414]. To achieve the required bond elongation, a laser scheme was proposed that implies population inversion and vibrational trapping in a dissociative state. In this work we identify two regimes where the scheme works, called the strong and the weak adiabatic regimes. We define appropriate parameters to identify the thresholds where the different regimes operate. The strong adiabatic regime is characterized by a quasi-static process that requires longer pulses. The molecule is stabilized at a bond distance and at a time directly controlled by the pulse in a time-symmetrical way. In this work we analyze the degree of control over the period and elongation of the bond as a function of the pulse bandwidth. The weak adiabatic regime implies dynamic deformation of the bond, which allows for larger bond stretch and the use of shorter pulses. The dynamics is anharmonic and not time-symmetrical and the final state is a wave packet in the ground potential. We show how the vibrational energy of the wave packet can be controlled by changing the pulse duration.