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Wonmuk Hwang

Publications and source records attributed to Wonmuk Hwang.

6 recordsLinked to original sources
PubMed2006

Atomistic simulation approach to a continuum description of self-assembled beta-sheet filaments.

We investigated the supramolecular structure and continuum mechanical properties of a beta-sheet nanofiber comprised of a self-assembling peptide ac-[RARADADA]2-am using computer simulations. The supramolecular structure was determined by constructing candidate filaments with dimensions compatible with those observed in atomic force microscopy and selecting the most stable ones after running molecular dynamics simulations on each of them. Four structures with different backbone hydrogen-bonding patterns were identified to be similarly stable. We then quantified the continuum mechanical properties of these identified structures by running three independent simulations: thermal motion analysis, normal mode analysis, and steered molecular dynamics. Within the range of deformations investigated, the filament showed linear elasticity in transverse directions with an estimated persistence length of 1.2-4.8 microm. Although side-chain interactions govern the propensity and energetics of filament self-assembly, we found that backbone hydrogen-bonding interactions are the primary determinant of filament elasticity, as demonstrated by its effective thickness, which is smaller than that estimated by atomic force microscopy or from the molecular geometry, as well as by the similar bending stiffness of a model filament without charged side chains. The generality of our approach suggests that it should be applicable to developing continuum elastic ribbon models of other beta-sheet filaments and amyloid fibrils.

Amino Acid Sequence↗
PubMed2005

Hierarchical self-assembly of a coiled-coil peptide into fractal structure.

Here we report the hierarchical self-assembly of a cross-linkable coiled-coil peptide containing an internal cysteine. Atomic force microscopy (AFM) experiments revealed the fractal structure of the assemblies, and molecular simulations showed that the peptides cross-linked to form clusters of coiled-coils, which further assembled to form globules of tens of nanometers in diameter. Such hierarchical organization was modulated by pH or thiol-reducing agent. Exploitation of the fractal structures through chemical methods may be valuable for the fabrication of materials spanning multiple length scales.

Computer Simulation↗
PubMed2004

Kinetic control of dimer structure formation in amyloid fibrillogenesis.

Amyloid fibril formation involves nonfibrillar oligomeric intermediates, which are important as possible cytotoxic species in neurodegenerative diseases. However, their transient nature and polydispersity have made it difficult to identify their formation mechanism or structure. We have investigated the dimerization process, the first step in aggregate formation, by multiple molecular dynamics simulations of five beta-sheet-forming peptides. Contrary to the regular beta-sheet structure of the amyloid fibril, the dimers exhibit all possible combinations of beta-sheets, with an overall preference for antiparallel arrangements. Through statistical analysis of 1,000 dimerization trajectories, each 1 ns in length, we have demonstrated that the observed distribution of dimer configurations is kinetically determined; hydrophobic interactions orient the peptides so as to minimize the solvent accessible surface area, and the dimer structures become trapped in energetically unfavorable conformations. Once the hydrophobic contacts are present, the backbone hydrogen bonds form rapidly by a zipper-like mechanism. The initial nonequilibrium structures formed are stable during the 1-ns simulation time for all five peptides at room temperature. In contrast, at higher temperatures, where rapid equilibration among different configurations occurs, the distribution follows the global energies. The relaxation time of dimers at room temperature was estimated to be longer than the time for diffusional encounters with other oligomers at typical concentrations. These results suggest that kinetic trapping could play a role in the structural evolution of early aggregates in amyloid fibrillogenesis.

Amyloid beta-Peptides↗
PubMed2004

Interfacial nano-structuring of designed peptides regulated by solution pH.

The in-situ conformations of peptide layers formed from the adsorption of two different synthetic 15-mer peptides at the hydrophilic silicon oxide/aqueous solution interface have been determined using neutron reflectivity (NR). The first peptide is based on the native sequence of a protein-binding domain within a heteromeric transcriptional activator, HAP2, identified from yeast Saccharomyces cerevisiae, with tyrosine (Y) present at the 1st, 8th and 15th amino acid positions, hence we denote this YYY15. Substitution of tryptophan (W) at the same locations gives WWW15. Both peptides have alpha-helical structure in phosphate buffer, as determined by circular dichroism (CD) spectra. D(2)O was used as solvent in the NR experiments to highlight structural heterogeneity across the hydrogenated peptide layers. At pH 7, YYY15 was found to form a weakly adsorbed interfacial monolayer. However, the mutant WWW15 showed strong interfacial adsorption, with the interfacial layer characterized by a middle hydrophobic sublayer of 7-8 A with lower scattering length density and two almost symmetrical hydrophilic outer sublayers of 6-8 A with higher scattering length density, suggesting the formation of a "sideways-on" helical conformation. An increase in pH to 9 resulted in the improved packing within the interfacial layer with similar structure. However, decrease in pH to 5 reduced the interfacial adsorption, mainly due to the enhanced solubility of the peptides associated with the protonation of arginine (R) and lysine (K) groups and the decreasing concentration of divalent HPO(4)(2-) in the phosphate buffer. Subsequent assessment of the reversibility of adsorption showed that once the peptide layers were formed they did not desorb. These interfacial structures may provide feasible routes to interfacial nano-templating.

Amino Acid Sequence↗