@article{latshaw_randolph_hall_2017, title={Aggregation of amphipathic peptides at an aqueous-organic interface using coarse-grained simulations}, volume={43}, ISSN={["1029-0435"]}, DOI={10.1080/08927022.2017.1319058}, abstractNote={Abstract The effect of an aqueous/organic interface on the folding and aggregation of amphipathic peptides is examined by applying discontinuous molecular dynamics (DMD) simulations combined with an intermediate resolution protein model, PRIME20, to a peptide/interface system. The systems contain 48 (KLLK)4 peptides in random coil or α-helical conformations interacting with both strong and weak interfaces. In the absence of an interface, most of the oligomers form helical bundles, a small fraction of which convert to β-sheets when the temperature is above the folding transition. Adding a weak interface decreases oligomer formation above the folding temperature and increases it below. Little monolayer formation is observed at the weak interface; instead reversible adsorption increases the local peptide concentration near the interface, promoting helical bundle formation in the aqueous phase below the folding temperature and β-sheet formation above the folding temperature. Introducing a strong interface leads to irreversible adsorption, promoting formation of helical monolayers below the folding temperature and mixed β-sheet/amorphous monolayers above the folding temperature. The (KLLK)4 peptide is more likely to adsorb to the interface when it is in an α-helical conformation, as opposed to a random coil, because of its larger hydrophobic moment.}, number={17}, journal={MOLECULAR SIMULATION}, author={Latshaw, David C., II and Randolph, Theodore W. and Hall, Carol K.}, year={2017}, pages={1448–1458} }
 @article{latshaw_hall_2015, title={Effects of Hydrophobic Macromolecular Crowders on Amyloid beta (16-22) Aggregation}, volume={109}, ISSN={["1542-0086"]}, DOI={10.1016/j.bpj.2015.05.032}, abstractNote={In Alzheimer's disease (AD), the amyloid β (Aβ) peptide aggregates in the brain to form progressively larger oligomers, fibrils, and plaques. The aggregation process is strongly influenced by the presence of other macromolecular species, called crowders, that can exert forces on the proteins. One very common attribute of macromolecular crowders is their hydrophobicity. We examined the effect of hydrophobic crowders on protein aggregation by using discontinuous molecular dynamics (DMD) simulations in combination with an intermediate resolution protein model, PRIME20. The systems considered contained 48 Aβ (16-22) peptides and crowders with diameters of 5 Å, 20 Å, and 40 Å, represented by hard spheres or spheres with square-well/square-shoulder interactions, at a crowder volume fraction of ϕ = 0.10. Results show that low levels of crowder hydrophobicity are capable of increasing the fibrillation lag time and high levels of crowder hydrophobicity can fully prevent the formation of fibrils. The types of structures that remain during the final stages of the simulations are summarized in a global phase diagram that shows fibril, disordered oligomer, or β-sheet phases in the space spanned by crowder size and crowder hydrophobicity. In particular, at high levels of hydrophobicity, simulations with 5 Å crowders result in only disordered oligomers and simulations with 40 Å crowders result in only β-sheets. The presence of hydrophobic crowders reduces the antiparallel β-sheet content of fibrils, whereas hard sphere crowders increase it. Finally, strong hydrophobic crowders alter the secondary structure of the Aβ (16-22) monomers, bending them into a shape that is incapable of forming ordered β-sheets or fibrils. These results qualitatively agree with previous theoretical and experimental work.}, number={1}, journal={BIOPHYSICAL JOURNAL}, author={Latshaw, David C., II and Hall, Carol K.}, year={2015}, month={Jul}, pages={124–134} }
 @article{latshaw_cheon_hall_2014, title={Effects of Macromolecular Crowding on Amyloid Beta (16-22) Aggregation Using Coarse-Grained Simulations}, volume={118}, ISSN={["1520-6106"]}, DOI={10.1021/jp508970q}, abstractNote={To examine the effect of crowding on protein aggregation, discontinuous molecular dynamics (DMD) simulations combined with an intermediate resolution protein model, PRIME20, were applied to a peptide/crowder system. The systems contained 192 Aβ(16–22) peptides and crowders of diameters 5, 20, and 40 Å, represented here by simple hard spheres, at crowder volume fractions of 0.00, 0.10, and 0.20. Results show that both crowder volume fraction and crowder diameter have a large impact on fibril and oligomer formation. The addition of crowders to a system of peptides increases the rate of oligomer formation, shifting from a slow ordered formation of oligomers in the absence of crowders, similar to nucleated polymerization, to a fast collapse of peptides and subsequent rearrangement characteristic of nucleated conformational conversion with a high maximum in the number of peptides in oligomers as the total crowder surface area increases. The rate of conversion from oligomers to fibrils also increases with increasing total crowder surface area, giving rise to an increased rate of fibril growth. In all cases, larger volume fractions and smaller crowders provide the greatest aggregation enhancement effects. We also show that the size of the crowders influences the formation of specific oligomer sizes. In our simulations, the 40 Å crowders enhance the number of dimers relative to the numbers of trimers, hexamers, pentamers, and hexamers, while the 5 Å crowders enhance the number of hexamers relative to the numbers of dimers, trimers, tetramers, and pentamers. These results are in qualitative agreement with previous experimental and theoretical work.}, number={47}, journal={JOURNAL OF PHYSICAL CHEMISTRY B}, author={Latshaw, David C. and Cheon, Mookyung and Hall, Carol K.}, year={2014}, month={Nov}, pages={13513–13526} }
 @article{higham_garber_latshaw_hall_pojman_khan_2014, title={Gelation and Cross-Linking in Multifunctional Thiol and Multifunctional Acrylate Systems Involving an in Situ Comonomer Catalyst}, volume={47}, ISSN={["1520-5835"]}, DOI={10.1021/ma402157f}, abstractNote={Dynamic rheology in combination with Fourier transform infrared spectroscopy (FTIR) is used to examine the gelation kinetics, mechanism, and gel point of novel thiol–acrylate systems containing varying concentrations of an in situ catalyst. Gelation, as evidenced from the gel time determined using the Winter–Chambon criterion, is found to occur more quickly with increasing catalyst concentration up until a critical catalyst concentration of 22 mol %, whereupon the gel time lengthens. Such a minimum in gel time may be attributed to changes in the number of available reaction sites and percentage conversion required for gelation. Chemical conversions at the gel point measured for representative samples are consistent with theoretical values calculated using Flory–Stockmayer’s statistical approach, confirming our hypothesis. Relaxation exponents of 0.97 and fractal dimensions of 1.3 are calculated for all samples, consistent with coarse-grained discontinuous molecular dynamics (DMD) simulations. The elevated...}, number={2}, journal={MACROMOLECULES}, author={Higham, Alina K. and Garber, Leah A. and Latshaw, David C., II and Hall, Carol K. and Pojman, John A. and Khan, Saad A.}, year={2014}, month={Jan}, pages={821–829} }