Soonmin Jang

Giant Flexoelectric Effect in Ferroelectric Epitaxial Thin Films

We report on nanoscale strain gradients in ferroelectric HoMnO(3) epitaxial thin films, resulting in a giant flexoelectric effect. Using grazing-incidence in-plane x-ray diffraction, we measured strain gradients in the films, which were 6 or 7 orders of magnitude larger than typical values reported for bulk oxides. The combination of transmission electron microscopy, electrical measurements, and electrostatic calculations showed that flexoelectricity provides a means of tuning the physical properties of ferroelectric epitaxial thin films, such as domain configurations and hysteresis curves.

Simulation Studies on the Stabilities of Aggregates Formed by Fibril-Forming Segments of α-Synuclein

Abstract We performed molecular dynamics simulations for various oligomers with different β-sheet conformations consisting of α-Synuclein 71–82 residues using an all atom force field and explicit water model. Tetramers of antiparallel β-sheet are shown to be stable, whereas parallel sheets are highly unstable due to the repulsive interactions between bulky and polar side chains as well as the weaker backbone hydrogen bonds. We also investigated the stabilities of double antiparallel β-sheets stacked with asymmetric and symmetric geometries. Our results show that this 12 amino acid residue peptide can form stable β-sheet conformers at 320K and higher temperatures. The backbone hydrogen bonds in β-sheet and the steric packing between hydrophobic side chains between β-sheets are shown to give conformational stabilities.

Computational Study on the Structural Diversity of Amyloid Beta Peptide (Aβ10-35) Oligomers

We studied the oligomerization of Alzheimer amyloid beta peptide (Abeta) using a replica exchange molecular dynamics (REMD) simulation. The simulation was performed with Abeta(10-35) dimers, trimers, and tetramers. Extensive REMD simulations illustrated several possible oligomer conformations. As the size of the oligomer increased from a dimer to a tetramer, the number of possible configurations was reduced. We identified all the possible conformations for each oligomer and characterized their temperature dependence. It was found that the detailed structures of the oligomers, which may act as folding intermediates, are highly sensitive to the parameters of the simulation environment such as temperature and concentration. Structural diversities of Abeta oligomers suggest multiple pathways of the aggregation process.

Conformational Characteristics of Unstructured Peptides: α-Synuclein

Abstract We have performed replica-exchange molecular dynamics simulations on 41 residue peptides containing NAC region of α-synuclein in various force fields and solvent conditions. Alpha-synuclein is known to be the major cause of Parkinsons disease by amyloid-like aggregation, and one of the natively unfolded proteins. To investigate conformational characteristics of intrinsically unstructured peptides, we carried out structural analysis by introducing ‘representative structure’ for ensemble of structures occurring during the overall trajectory. Representative structures may be defined by using either coordinate averaging or distance averaging. When applied to the natively folded proteins such as villin headpiece, structural analysis based on representative structure was found to yield consistent results with those obtained from conventional analysis. Individual conformations obtained from the simulations of NAC peptide for various conditions show flexible structures close to random coil. Secondary structure contents and free energy surfaces showed dependency on solvent conditions, which may be interpreted as another manifestation of structural diversity. It is found that representative structures can provide useful information about structural characteristics of intrinsically unstructured proteins.

Free energy surfaces of miniproteins with a ββα motif: Replica exchange molecular dynamics simulation with an implicit solvation model

Designed miniproteins with a ββα motif, such as BBA5, 1FSD, and 1PSV can serve as a benchmark set to test the validity of all‐atom force fields with computer simulation, because they contain all the basic structural elements in protein folding. Unfortunately, it was found that the standard all‐atom force fields with the generalized Born (GB) implicit solvation model tend to produce distorted free energy surfaces for the ββα proteins, not only because energetically those proteins need to be described by more balanced weights of the α‐ and β‐strands, but also because the GB implicit solvation model suffers from overestimated salt bridge effects. In an attempt to resolve these problems, we have modified one of the standard all‐atom force fields in conjunction with the GB model, such that each native state of the ββα proteins is in its free energy minimum state with reasonable energy barriers separating local minima. With this modified energy model, the free energy contour map in each protein was constructed from the replica exchange molecular dynamics REMD simulation. The resulting free energy surfaces are significantly improved in comparison with previous simulation results and consistent with general views on small protein folding behaviors with realistic topology and energetics of all three proteins. Proteins 2006.

Direct folding simulation of α‐helices and β‐hairpins based on a single all‐atom force field with an implicit solvation model

Recently, we have shown that a modified energy model based on the param99 force field with the generalized Born (GB) solvation model produces reliable free energy landscapes of mini‐proteins with a ββα motif (BBA5, 1FSD, and 1PSV), with the native structures of the mini‐proteins located in their lowest free energy minimum states. One of the main features in the modified energy model is a significant improvement for more balanced treatments of α and β strands in proteins. In this study, using the replica exchange molecular dynamics (REMD) simulation method with this new force field, we have carried out extensive ab initio folding studies of several well‐known peptides with α or β strands (C‐peptide, EK‐peptide, le0q, and gbl). Starting from fully extended conformations as the initial conditions, all of the native‐like structures of the target peptides were successfully identified by REMD, with reasonable representations of free energy surfaces. The present simulation results with the modified energy model are consistent with experiments, demonstrating an extended applicability of the energy model to folding studies of a variety of α‐helices, β‐strands, and α/β proteins. Proteins 2007.

On the classical theory of the rate of isomerization of HCN

We report the results of calculations, using classical mechanics, of the rate of the isomerization reaction HCN↔CNH. The three purposes of the calculations are (i) to test whether or not the Zhao–Rice approximate version of the Davis–Gray theory provides an accurate description of the rate of isomerization when there is a large scale atomic rearrangement; (ii) to determine if the quasi‐two‐dimensional reaction path representation of dynamical evolution on a multidimensional potential energy surface preserves the major features of the phase space mappings in two dimensions that are the key features of the Davis–Gray formulation of unimolecular reaction rate theory; and (iii) to determine if the reaction path representation is useful when the energy of the system is considerably greater than that along the minimum energy path. We find that both the Zhao–Rice (ZR) and the reaction path calculations of the isomerization rate constant are in reasonable agreement with the rate constant estimated from trajectory...

Consistent free energy landscapes and thermodynamic properties of small proteins based on a single all-atom force field employing an implicit solvation

We have attempted to improve the PARAM99 force field in conjunction with the generalized Born (GB) solvation model with a surface area correction for more consistent protein folding simulations. For this purpose, using an extended alphabeta training set of five well-studied molecules with various folds (alpha, beta, and betabetaalpha), a previously modified version of PARAM99/GBSA is further refined, such that all native states of the five training species correspond to their lowest free energy minimum states. The resulting modified force field (PARAM99MOD5/GBSA) clearly produces reasonably acceptable conformational free energy surfaces of the training set with correct identifications of their native states in the free energy minimum states. Moreover, due to its well-balanced nature, this new force field is expected to describe secondary structure propensities of diverse folds in a more consistent manner. Remarkably, temperature dependent behaviors simulated with the current force field are in good agreement with the experiment. This agreement is a significant improvement over the existing standard all-atom force fields. In addition, fundamentally important thermodynamic quantities, such as folding enthalpy (DeltaH) and entropy (DeltaS), agree reasonably well with the experimental data.

A fully atomistic computer simulation study of cold denaturation of a β-hairpin

Cold denaturation is a fundamental phenomenon in aqueous solutions where the native structure of proteins disrupts on cooling. Understanding this process in molecular details can provide a new insight into the detailed natures of hydrophobic forces governing the stability of proteins in water. We show that the cold-denaturation-like phenomenon can be directly observed at low temperatures using a fully atomistic molecular dynamics simulation method. Using a highly optimized protein force field in conjunction with three different explicit water models, a replica exchange molecular dynamics simulation scheme at constant pressures allows for the computation of the melting profile of an experimentally well-characterized β-hairpin peptide. For all three water models tested, the simulated melting profiles are indicative of possible cold denaturation. From the analysis of simulation ensembles, we find that the most probable cold-denatured structure is structurally compact, with its hydrogen bonds and native hydrophobic packing substantially disrupted.

All-atom level direct folding simulation of a ββα miniprotein

We performed ab initio folding simulation for a betabetaalpha peptide BBA5 (PDB code 1T8J) with a modified param99 force field using the generalized Born solvation model (param99MOD5/GBSA). For efficient conformational sampling, we extended a previously developed novel Q-replica exchange molecular dynamics (Q-REMD) into a multiplexed Q-REMD. Starting from a fully extended conformation, we were able to locate the nativelike structure in the global free minimum region at 280 K. The current approach, which combines the more balanced force field with the efficient sampling scheme, demonstrates a clear advantage in direct folding simulation at all-atom level.