@misc{nguyen_ramamoorthy_sahoo_zheng_faller_straub_dominguez_shea_dokholyan_de simone_et al._2021, title={Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis}, volume={121}, ISSN={["1520-6890"]}, DOI={10.1021/acs.chemrev.0c01122}, abstractNote={Protein misfolding and aggregation is observed in many amyloidogenic diseases affecting either the central nervous system or a variety of peripheral tissues. Structural and dynamic characterization of all species along the pathways from monomers to fibrils is challenging by experimental and computational means because they involve intrinsically disordered proteins in most diseases. Yet understanding how amyloid species become toxic is the challenge in developing a treatment for these diseases. Here we review what computer, in vitro, in vivo, and pharmacological experiments tell us about the accumulation and deposition of the oligomers of the (Aβ, tau), α-synuclein, IAPP, and superoxide dismutase 1 proteins, which have been the mainstream concept underlying Alzheimer's disease (AD), Parkinson's disease (PD), type II diabetes (T2D), and amyotrophic lateral sclerosis (ALS) research, respectively, for many years.}, number={4}, journal={CHEMICAL REVIEWS}, author={Nguyen, Phuong H. and Ramamoorthy, Ayyalusamy and Sahoo, Bikash R. and Zheng, Jie and Faller, Peter and Straub, John E. and Dominguez, Laura and Shea, Joan-Emma and Dokholyan, Nikolay V and De Simone, Alfonso and et al.}, year={2021}, month={Feb}, pages={2545–2647} }
 @article{wong_shao_wang_seroski_liu_lint_hudalla_hall_paravastu_2021, title={CATCH Peptides Coassemble into Structurally Heterogeneous beta-Sheet Nanofibers with Little Preference to beta-Strand Alignment}, volume={125}, ISSN={["1520-5207"]}, DOI={10.1021/acs.jpcb.0c11645}, abstractNote={Coassembling peptides offer an additional degree of freedom in the design of nanostructured biomaterials when compared to analogous self-assembling peptides. Yet, our understanding of how amino acid sequences encodes coassembled nanofiber structure is limited. Prior work on a charge-complementary pair, CATCH+ and CATCH- peptides, detected like-peptide nearest neighbors (CATCH+:CATCH+ and CATCH-:CATCH-) within coassembled β-sheet nanofibers; these self-associated peptide pairs marked a departure from an "ideal" coassembled structure. In this work, we employ solid-state NMR, isotope-edited FTIR, and coarse-grained molecular dynamics simulations to evaluate the alignment of β-strands within CATCH peptide nanofibers. Both experimental and computational results suggest that CATCH molecules coassemble into structurally heterogeneous nanofibers, which is consistent with our observations in another coassembling system, the King-Webb peptides. Within β-sheet nanofibers, β-strands were found to have nearest neighbors aligned in-register parallel, in-register antiparallel, and out-of-register. In comparison to the King-Webb peptides, CATCH nanofibers exhibit a greater degree of structural heterogeneity. By comparing the amino acid sequences of CATCH and King-Webb peptides, we can begin to unravel sequence-to-structure relationships, which may encode more precise coassembled β-sheet nanostructures.}, number={16}, journal={JOURNAL OF PHYSICAL CHEMISTRY B}, author={Wong, Kong M. and Shao, Qing and Wang, Yiming and Seroski, Dillon T. and Liu, Renjie and Lint, Annabelle H. and Hudalla, Gregory A. and Hall, Carol K. and Paravastu, Anant K.}, year={2021}, month={Apr}, pages={4004–4015} }
 @article{xiao_wang_seroski_wong_liu_paravastu_hudalla_hall_2021, title={De novo design of peptides that coassemble into beta sheet-based nanofibrils}, volume={7}, ISSN={["2375-2548"]}, DOI={10.1126/sciadv.abf7668}, abstractNote={Computational discoveries and experimental characterizations of coassembly peptides that form β sheet–based nanofibrils.}, number={36}, journal={SCIENCE ADVANCES}, author={Xiao, Xingqing and Wang, Yiming and Seroski, Dillon T. and Wong, Kong M. and Liu, Renjie and Paravastu, Anant K. and Hudalla, Gregory A. and Hall, Carol K.}, year={2021}, month={Sep} }
 @article{wong_robang_lint_wang_dong_xiao_seroski_liu_shao_hudalla_et al._2021, title={Engineering beta-Sheet Peptide Coassemblies for Biomaterial Applications}, volume={12}, ISSN={["1520-5207"]}, DOI={10.1021/acs.jpcb.1c04873}, abstractNote={Peptide coassembly, wherein at least two different peptides interact to form multicomponent nanostructures, is an attractive approach for generating functional biomaterials. Current efforts seek to design pairs of peptides, A and B, that form nanostructures (e.g., β-sheets with ABABA-type β-strand patterning) while resisting self-assembly (e.g., AAAAA-type or BBBBB-type β-sheets). To confer coassembly behavior, most existing designs have been based on highly charged variants of known self-assembling peptides; like-charge repulsion limits self-assembly while opposite-charge attraction promotes coassembly. Recent analyses using solid-state NMR and coarse-grained simulations reveal that preconceived notions of structure and molecular organization are not always correct. This perspective highlights recent advances and key challenges to understanding and controlling peptide coassembly.}, journal={JOURNAL OF PHYSICAL CHEMISTRY B}, author={Wong, Kong M. and Robang, Alicia S. and Lint, Annabelle H. and Wang, Yiming and Dong, Xin and Xiao, Xingqing and Seroski, Dillon T. and Liu, Renjie and Shao, Qing and Hudalla, Gregory A. and et al.}, year={2021}, month={Dec} }
 @article{bunce_wang_radford_wilson_hall_2021, title={Structural insights into peptide self-assembly using photo-induced crosslinking experiments and discontinuous molecular dynamics}, volume={67}, ISSN={["1547-5905"]}, DOI={10.1002/aic.17101}, abstractNote={Abstract}, number={3}, journal={AICHE JOURNAL}, author={Bunce, Samuel J. and Wang, Yiming and Radford, Sheena E. and Wilson, Andrew J. and Hall, Carol K.}, year={2021}, month={Mar} }
 @article{shao_wong_seroski_wang_liu_paravastu_hudalla_hall_2020, title={Anatomy of a selectively coassembled beta-sheet peptide nanofiber}, volume={117}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1912810117}, abstractNote={
            Peptide self-assembly, wherein molecule A associates with other A molecules to form fibrillar β-sheet structures, is common in nature and widely used to fabricate synthetic biomaterials. Selective coassembly of peptide pairs A and B with complementary partial charges is gaining interest due to its potential for expanding the form and function of biomaterials that can be realized. It has been hypothesized that charge-complementary peptides organize into alternating ABAB-type arrangements within assembled β-sheets, but no direct molecular-level evidence exists to support this interpretation. We report a computational and experimental approach to characterize molecular-level organization of the established peptide pair, CATCH. Discontinuous molecular dynamics simulations predict that CATCH(+) and CATCH(−) peptides coassemble but do not self-assemble. Two-layer β-sheet amyloid structures predominate, but off-pathway β-barrel oligomers are also predicted. At low concentration, transmission electron microscopy and dynamic light scattering identified nonfibrillar ∼20-nm oligomers, while at high concentrations elongated fibers predominated. Thioflavin T fluorimetry estimates rapid and near-stoichiometric coassembly of CATCH(+) and CATCH(−) at concentrations ≥100 μM. Natural abundance
            13
            C NMR and isotope-edited Fourier transform infrared spectroscopy indicate that CATCH(+) and CATCH(−) coassemble into two-component nanofibers instead of self-sorting. However,
            13
            C–
            13
            C dipolar recoupling solid-state NMR measurements also identify nonnegligible AA and BB interactions among a majority of AB pairs. Collectively, these results demonstrate that strictly alternating arrangements of β-strands predominate in coassembled CATCH structures, but deviations from perfect alternation occur. Off-pathway β-barrel oligomers are also suggested to occur in coassembled β-strand peptide systems.
          }, number={9}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Shao, Qing and Wong, Kong M. and Seroski, Dillon T. and Wang, Yiming and Liu, Renjie and Paravastu, Anant K. and Hudalla, Gregory A. and Hall, Carol K.}, year={2020}, month={Mar}, pages={4710–4717} }
 @article{wang_wang_hall_2020, title={Development of a coarse-grained lipid model, LIME 2.0, for DSPE using multistate iterative Boltzmann inversion and discontinuous molecular dynamics simulations}, volume={521}, ISSN={["1879-0224"]}, DOI={10.1016/j.fluid.2020.112704}, abstractNote={We suggest an improved version of the intermediate resolution implicit solvent model for lipids, LIME, that was previously developed for use with discontinuous molecular dynamics (DMD) simulations. LIME gets its geometrical and energy parameters between bonded and nonbonded pairs of coarse-grained (CG) sites from atomistic simulations. The improved model, LIME 2.0, uses multiple square wells rather than the single square well used in original LIME to obtain intermolecular interactions that more faithfully mimic those from atomistic simulations. The multi-state iterative Boltzmann inversion (MS-IBI) scheme is used to determine the interaction parameters. This means that a single set of interaction parameters between coarse-grained sites can be used to represent the lipid bilayers at different temperatures. The physical properties of CG DSPE lipid bilayer are calculated using CG simulations and compared to atomistic simulations results to verify the improved model. The phase transition temperature of the lipid bilayer is measured accurately and the lipid translocation phenomenon, “flip-flop” is observed through CG simulation. These results suggest that CG parameterization using multiple square-wells and the MS-IBI scheme is well suited to the study of lipid bilayers across a range of temperatures with DMD simulations.}, journal={FLUID PHASE EQUILIBRIA}, author={Wang, Kye Won and Wang, Yiming and Hall, Carol K.}, year={2020}, month={Oct} }
 @article{wong_wang_seroski_larkin_mehta_hudalla_hall_paravastu_2020, title={Molecular complementarity and structural heterogeneity within co-assembled peptide beta-sheet nanofibers}, volume={12}, ISSN={["2040-3372"]}, DOI={10.1039/c9nr08725g}, abstractNote={Charge-complementary peptides organize into co-assembled β-sheet nanofibers composed of multiple substructures rather than a single structure as seen in self-assembling peptides.}, number={7}, journal={NANOSCALE}, author={Wong, Kong M. and Wang, Yiming and Seroski, Dillon T. and Larkin, Grant E. and Mehta, Anil K. and Hudalla, Gregory A. and Hall, Carol K. and Paravastu, Anant K.}, year={2020}, month={Feb}, pages={4506–4518} }
 @article{patterson-orazem_hill_wang_dominic_hall_lieberman_2019, title={Differential Misfolding Properties of Glaucoma-Associated Olfactomedin Domains from Humans and Mice}, volume={58}, ISSN={["0006-2960"]}, DOI={10.1021/acs.biochem.8b01309}, abstractNote={Mutations in myocilin, predominantly within its olfactomedin (OLF) domain, are causative for the heritable form of open angle glaucoma in humans. Surprisingly, mice expressing Tyr423His mutant myocilin, corresponding to a severe glaucoma-causing mutation (Tyr437His) in human subjects, exhibit a weak, if any, glaucoma phenotype. To address possible protein-level discrepancies between mouse and human OLFs, which might lead to this outcome, biophysical properties of mouse OLF were characterized for comparison with those of human OLF. The 1.55 Å resolution crystal structure of mouse OLF reveals an asymmetric 5-bladed β-propeller that is nearly indistinguishable from previous structures of human OLF. Wild-type and selected mutant mouse OLFs mirror thermal stabilities of their human OLF counterparts, including characteristic stabilization in the presence of calcium. Mouse OLF forms thioflavin T-positive aggregates with a similar end-point morphology as human OLF, but amyloid aggregation kinetic rates of mouse OLF are faster than human OLF. Simulations and experiments support the interpretation that kinetics of mouse OLF are faster because of a decreased charge repulsion arising from more neutral surface electrostatics. Taken together, phenotypic differences observed in mouse and human studies of mutant myocilin could be a function of aggregation kinetics rates, which would alter the lifetime of putatively toxic protofibrillar intermediates.}, number={13}, journal={BIOCHEMISTRY}, author={Patterson-Orazem, Athena C. and Hill, Shannon E. and Wang, Yiming and Dominic, Iramofu M. and Hall, Carol K. and Lieberman, Raquel L.}, year={2019}, month={Apr}, pages={1718–1727} }
 @article{bunce_wang_stewart_ashcroft_radford_hall_wilson_2019, title={Molecular insights into the surface-catalyzed secondary nucleation of amyloid-beta(40) (A beta(40)) by the peptide fragment A beta(16-22)}, volume={5}, ISSN={["2375-2548"]}, DOI={10.1126/sciadv.aav8216}, abstractNote={Combined experiment and simulation reveals a structural mechanism of surface-catalyzed nucleation in Aβ amyloid formation.}, number={6}, journal={SCIENCE ADVANCES}, author={Bunce, Samuel J. and Wang, Yiming and Stewart, Katie L. and Ashcroft, Alison E. and Radford, Sheena E. and Hall, Carol K. and Wilson, Andrew J.}, year={2019}, month={Jun} }
 @article{wang_bunce_radford_wilson_auer_hall_2019, title={Thermodynamic phase diagram of amyloid-β (16–22) peptide}, volume={116}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.1819592116}, DOI={10.1073/pnas.1819592116}, abstractNote={Significance}, number={6}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Wang, Yiming and Bunce, Samuel J. and Radford, Sheena E. and Wilson, Andrew J. and Auer, Stefan and Hall, Carol K.}, year={2019}, month={Feb}, pages={2091–2096} }
 @article{wang_hall_2018, title={Seeding and cross-seeding fibrillation of N-terminal prion protein peptides PrP(120-144)}, volume={27}, ISSN={0961-8368}, url={http://dx.doi.org/10.1002/pro.3421}, DOI={10.1002/pro.3421}, abstractNote={Abstract}, number={7}, journal={Protein Science}, publisher={Wiley}, author={Wang, Yiming and Hall, Carol K.}, year={2018}, month={May}, pages={1304–1313} }
 @article{wang_gao_hill_huard_tomlin_lieberman_paravastu_hall_2018, title={Simulations and Experiments Delineate Amyloid Fibrilization by Peptides Derived from Glaucoma-Associated Myocilin}, volume={122}, ISSN={["1520-6106"]}, DOI={10.1021/acs.jpcb.8b03000}, abstractNote={Mutant myocilin aggregation is associated with inherited open angle glaucoma, a prevalent optic neuropathy leading to blindness. Comprehension of mutant myocilin aggregation is of fundamental importance to glaucoma pathogenesis and ties glaucoma to amyloid diseases such as Alzheimer's. Here, we probe the aggregation properties of peptides derived from the myocilin olfactomedin domain. Peptides P1 (residues 326-337) and P3 (residues 426-442) were identified previously to form amyloids. Coarse-grained discontinuous molecular dynamics simulations using the PRIME20 force field (DMD/PRIME20) predict that P1 and P3 are aggregation-prone; P1 consistently forms fibrillar aggregates with parallel in-register β-sheets, whereas P3 forms β-sheet-containing aggregates without distinct order. Natural abundance 13C solid-state NMR spectra validate that aggregated P1 exhibits amyloid signatures and is more homogeneous than aggregated P3. DMD/PRIME20 simulations provide a viable method to predict peptide aggregation propensities and aggregate structure/order which cannot be accessed by bioinformatics or readily attained experimentally.}, number={22}, journal={JOURNAL OF PHYSICAL CHEMISTRY B}, author={Wang, Yiming and Gao, Yuan and Hill, Shannon E. and Huard, Dustin J. E. and Tomlin, Moya O. and Lieberman, Raquel L. and Paravastu, Anant K. and Hall, Carol K.}, year={2018}, month={Jun}, pages={5845–5850} }
 @article{wang_latshaw_hall_2017, title={Aggregation of A beta(17-36) in the Presence of Naturally Occurring Phenolic Inhibitors Using Coarse-Grained Simulations}, volume={429}, ISSN={["1089-8638"]}, DOI={10.1016/j.jmb.2017.10.006}, abstractNote={Although some naturally occurring polyphenols have been found to inhibit amyloid β (Aβ) fibril formation and reduce neuron cell toxicity in vitro, their exact inhibitory mechanism is unknown. In this work, discontinuous molecular dynamics combined with the PRIME20 force field and a newly built inhibitor model are performed to examine the effect of vanillin, resveratrol, curcumin, and epigallocatechin-3-gallate (EGCG) on the aggregation of Aβ(17-36) peptides. Four sets of peptide/inhibitor simulations are performed in which inhibitors (1) bind to Aβ(17-36) monomer (2) interfere with Aβ(17-36) oligomerization (3) disrupt a pre-formed Aβ(17-36) protofilament, and (4) prevent the growth of Aβ(17-36) protofilament. The single-ring compound, vanillin, slightly slows down but cannot inhibit the formation of a U-shaped Aβ(17-36) protofilament. The multiple-ring compounds, EGCG, resveratrol, and curcumin, redirect Aβ(17-36) from a fibrillar aggregate to an unstructured oligomer. The three aromatic groups of the EGCG molecule are in a stereo (nonplanar) configuration, helping it contact the N-terminal, middle, and C-terminal regions of the peptide. Resveratrol and curcumin bind only to the hydrophobic residues near peptide termini. The rank order of inhibitory effectiveness of Aβ(17-36) aggregation is as follows: EGCG > resveratrol > curcumin > vanillin, consistent with experimental findings on inhibiting full-length Aβ fibrillation. Furthermore, we learn that the inhibition effect of EGCG is specific to the peptide sequence, while those of resveratrol and curcumin are non-specific in that they stem from strong interference with hydrophobic side-chain association, regardless of the residues' location and peptide sequence. Our studies provide molecular-level insights into how polyphenols inhibit Aβ fibril formation, knowledge that could be useful for designing amyloid inhibitors.}, number={24}, journal={JOURNAL OF MOLECULAR BIOLOGY}, author={Wang, Yiming and Latshaw, David C. and Hall, Carol K.}, year={2017}, month={Dec}, pages={3893–3908} }
 @article{xiao_wang_leonard_hall_2017, title={Extended Concerted Rotation Technique Enhances the Sampling Efficiency of the Computational Peptide-Design Algorithm}, volume={13}, ISSN={["1549-9626"]}, DOI={10.1021/acs.jctc.7b00714}, abstractNote={To enhance the sampling efficiency of our computational peptide-design algorithm in conformational space, the concerted rotation (CONROT) technique is extended to enable larger conformational perturbations of peptide chains. This allows us to make relatively large peptide conformation changes during the process of designing peptide sequences to bind with high affinity to a specific target. Searches conducted using the new algorithm identified six potential λ N(2-22) peptide variants, called B1-B6, which bind to boxB RNA with high affinity. The results of explicit-solvent atomistic molecular dynamics simulations revealed that four of the evolved peptides, viz. B1, B2, B3, and B5, are excellent candidate binders to the target boxB RNA as they have lower binding free energies than the original λ N(2-22) peptide. Three of the four peptides, B2, B3, and B5, result from searches that contain both sequence and conformation changes, indicating that adding backbone motif changes to the peptide-design algorithm improves its performance considerably.}, number={11}, journal={JOURNAL OF CHEMICAL THEORY AND COMPUTATION}, author={Xiao, Xingqing and Wang, Yiming and Leonard, Joshua N. and Hall, Carol K.}, year={2017}, month={Nov}, pages={5709–5720} }
 @article{wang_shao_hall_2016, title={N-terminal Prion Protein Peptides (PrP(120-144)) Form Parallel In-register beta-Sheets via Multiple Nucleation-dependent Pathways}, volume={291}, ISSN={["1083-351X"]}, DOI={10.1074/jbc.m116.744573}, abstractNote={The prion diseases are a family of fatal neurodegenerative diseases associated with the misfolding and accumulation of normal prion protein (PrPC) into its pathogenic scrapie form (PrPSc). Understanding the fundamentals of prion protein aggregation and the molecular architecture of PrPSc is key to unraveling the pathology of prion diseases. Our work investigates the early-stage aggregation of three prion protein peptides, corresponding to residues 120–144 of human (Hu), bank vole (BV), and Syrian hamster (SHa) prion protein, from disordered monomers to β-sheet-rich fibrillar structures. Using 12 μs discontinuous molecular dynamics simulations combined with the PRIME20 force field, we find that the Hu-, BV-, and SHaPrP(120–144) aggregate via multiple nucleation-dependent pathways to form U-shaped, S-shaped, and Ω-shaped protofilaments. The S-shaped HuPrP(120–144) protofilament is similar to the amyloid core structure of HuPrP(112–141) predicted by Zweckstetter. HuPrP(120–144) has a shorter aggregation lag phase than BVPrP(120–144) followed by SHaPrP(120–144), consistent with experimental findings. Two amino acid substitutions I138M and I139M retard the formation of parallel in-register β-sheet dimers during the nucleation stage by increasing side chain-side chain association and reducing side chain interaction specificity. On average, HuPrP(120–144) aggregates contain more parallel β-sheet content than those formed by BV- and SHaPrP(120–144). Deletion of the C-terminal residues 138–144 prevents formation of fibrillar structures in agreement with the experiment. This work sheds light on the amyloid core structures underlying prion strains and how I138M, I139M, and S143N affect prion protein aggregation kinetics.}, number={42}, journal={JOURNAL OF BIOLOGICAL CHEMISTRY}, author={Wang, Yiming and Shao, Qing and Hall, Carol K.}, year={2016}, month={Oct}, pages={22093–22105} }