@article{chen_shao_hall_2023, title={Effect of sequence pattern on conformation of DOPA-Peptide conjugate aggregates: a discontinuous molecular dynamics simulation study}, volume={8}, ISSN={["1029-0435"]}, DOI={10.1080/08927022.2023.2240911}, abstractNote={ABSTRACT Underwater adhesives are critical for many applications, including marine coatings, sealants, and medical devices. Research on natural underwater adhesives has shown that L-3,4-dihydroxyphenylalanine (DOPA) and amyloid nanostructures are vital to their adhesive abilities. The fusion of DOPA-containing chains and amyloid-forming peptides creates a new space for designing underwater adhesives capable of multi-surface adhesion. One critical question for this design is the interplay between the DOPA and amyloid-forming peptide regions. Here we investigate the effect of the sequence pattern of DOPA-containing chains on the aggregation conformation of conjugates. Discontinuous molecular dynamics simulations were performed for fourteen DOPA-amyloid conjugates with different sequence patterns along the DOPA-containing portion. The amyloid-forming portion is represented by KLVFFAE from the Aβ42 peptide. The structural properties of the DOPA-amyloid conjugates are characterised by the percentages of ordered secondary structures and residue-residue contact maps. The results showed that certain patterns of DOPA and glycine in the DOPA-containing tail allowed the KLVFFAE portions of the conjugates to form distinct ordered β-sheets, and the DOPA-containing portion and the KLVFFAE portion of the conjugates to remain separated both within the same chain and amongst different chains. Among the designs, the most promising sequences are KLVFFAE-G-YYGYYGYY (where Y represents DOPA) and KLVFFAE-G-YYYYGGGG.}, journal={MOLECULAR SIMULATION}, author={Chen, Amelia B. and Shao, Qing and Hall, Carol K.}, year={2023}, month={Aug} }
 @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{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={Significance Coassembly, in which peptides A and B selectively associate to form β-sheet structures, is an emerging approach to fabricate multicomponent biomaterials. As coassembly is rare in nature, designing synthetic peptide pairs must be informed by insights into molecular organization within existing systems. For charge-complementary peptide pairs, it is assumed that molecules organize into an alternating arrangement, yet there are no experimental data to support this assumption. Here, a combination of molecular dynamics simulations, biophysical measurements, electron microscopy, and solid-state NMR demonstrates that an established pair of charge-complementary peptides [CATCH(+) and CATCH(−)] coassemble into bilayers of AB-alternating β-sheets. However, significant mismatched AA and BB neighbors do occur. Off-pathway β-barrel oligomers were predicted by simulations, and concentration-dependent oligomer formation was observed experimentally. 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 13C NMR and isotope-edited Fourier transform infrared spectroscopy indicate that CATCH(+) and CATCH(−) coassemble into two-component nanofibers instead of self-sorting. However, 13C–13C 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{seroski_dong_wong_liu_shao_paravastu_hall_hudalla_2020, title={Charge guides pathway selection in beta-sheet fibrillizing peptide co-assembly}, volume={3}, ISSN={["2399-3669"]}, DOI={10.1038/s42004-020-00414-w}, abstractNote={Abstract Peptide co-assembly is attractive for creating biomaterials with new forms and functions. Emergence of these properties depends on the peptide content of the final assembled structure, which is difficult to predict in multicomponent systems. Here using experiments and simulations we show that charge governs content by affecting propensity for self- and co-association in binary CATCH(+/−) peptide systems. Equimolar mixtures of CATCH(2+/2−), CATCH(4+/4−), and CATCH(6+/6−) formed two-component β-sheets. Solid-state NMR suggested the cationic peptide predominated in the final assemblies. The cationic-to-anionic peptide ratio decreased with increasing charge. CATCH(2+) formed β-sheets when alone, whereas the other peptides remained unassembled. Fibrillization rate increased with peptide charge. The zwitterionic CATCH parent peptide, “Q11”, assembled slowly and only at decreased simulation temperature. These results demonstrate that increasing charge draws complementary peptides together faster, favoring co-assembly, while like-charged molecules repel. We foresee these insights enabling development of co-assembled peptide biomaterials with defined content and predictable properties.}, number={1}, journal={COMMUNICATIONS CHEMISTRY}, author={Seroski, Dillon T. and Dong, Xin and Wong, Kong M. and Liu, Renjie and Shao, Qing and Paravastu, Anant K. and Hall, Carol K. and Hudalla, Gregory A.}, year={2020}, month={Nov} }
 @article{shao_hall_2018, title={Selectivity of Glycine for Facets on Gold Nanoparticles}, volume={122}, ISSN={["1520-6106"]}, DOI={10.1021/acs.jpcb.7b10677}, abstractNote={The performance of nanoparticles in medical applications depends on their interactions with various molecules. Despite extensive research on this subject, it remains unclear where on an inhomogeneous nanoparticle molecules prefer to adsorb. Here we investigate the selectivity of glycine molecules for facets on five bare gold nanoparticles with diameters from 1.0 to 5.0 nm. Well-tempered metadynamics simulations are conducted to calculate the adsorption free-energy landscapes of a glycine molecule on various locations for the five gold nanoparticles in explicit water. We also calculate the glycine molecule's adsorption free energies on the five gold nanoparticles in vacuum and on three flat gold surfaces as a reference. The simulation results show that glycine molecules prefer to adsorb on the (110) facet for the 1.0 and 2.0 nm nanoparticles, the edges for the 3.0 nm nanoparticle, and the (111) facet for the 4.0 and 5.0 nm nanoparticles in water. The effect of water solvent on the selectivity is investigated through comparing the adsorption free-energy landscapes for glycine molecules on the nanoparticles in water and in vacuum. The area of the facet plays a key role in determining the selectivity of glycine molecules for the different facets, especially the shift of the selectivity as the nanoparticle diameter changes. Our simulations suggest that nanoparticle size and shape can be engineered to control the preferred adsorption location of molecules.}, number={13}, journal={JOURNAL OF PHYSICAL CHEMISTRY B}, author={Shao, Qing and Hall, Carol K.}, year={2018}, month={Apr}, pages={3491–3499} }
 @article{shao_hall_2017, title={Allosteric effects of gold nanoparticles on human serum albumin}, volume={9}, ISSN={["2040-3372"]}, DOI={10.1039/c6nr07665c}, abstractNote={The ability of nanoparticles to alter protein structure and dynamics plays an important role in their medical and biological applications. We investigate allosteric effects of gold nanoparticles on human serum albumin protein using molecular simulations. The extent to which bound nanoparticles influence the structure and dynamics of residues distant from the binding site is analyzed. The root mean square deviation, root mean square fluctuation and variation in the secondary structure of individual residues on a human serum albumin protein are calculated for four protein-gold nanoparticle binding complexes. The complexes are identified in a brute-force search process using an implicit-solvent coarse-grained model for proteins and nanoparticles. They are then converted to atomic resolution and their structural and dynamic properties are investigated using explicit-solvent atomistic molecular dynamics simulations. The results show that even though the albumin protein remains in a folded structure, the presence of a gold nanoparticle can cause more than 50% of the residues to decrease their flexibility significantly, and approximately 10% of the residues to change their secondary structure. These affected residues are distributed on the whole protein, even on regions that are distant from the nanoparticle. We analyze the changes in structure and flexibility of amino acid residues on a variety of binding sites on albumin and confirm that nanoparticles could allosterically affect the ability of albumin to bind fatty acids, thyroxin and metals. Our simulations suggest that allosteric effects must be considered when designing and deploying nanoparticles in medical and biological applications that depend on protein-nanoparticle interactions.}, number={1}, journal={NANOSCALE}, author={Shao, Qing and Hall, Carol K.}, year={2017}, month={Jan}, pages={380–390} }
 @inbook{shao_hall_2016, title={A Discontinuous Potential Model for Protein–Protein Interactions}, ISBN={9789811011269 9789811011283}, ISSN={2364-5083 2364-5091}, url={http://dx.doi.org/10.1007/978-981-10-1128-3_1}, DOI={10.1007/978-981-10-1128-3_1}, abstractNote={Protein–protein interactions play an important role in many biologic and industrial processes. In this work, we develop a two-bead-per-residue model that enables us to account for protein–protein interactions in a multi-protein system using discontinuous molecular dynamics simulations. This model deploys discontinuous potentials to describe the non-bonded interactions and virtual bonds to keep proteins in their native state. The geometric and energetic parameters are derived from the potentials of mean force between sidechain–sidechain, sidechain–backbone, and backbone–backbone pairs. The energetic parameters are scaled with the aim of matching the second virial coefficient of lysozyme reported in experiment. We also investigate the performance of several bond-building strategies.}, booktitle={Foundations of Molecular Modeling and Simulation}, publisher={Springer Singapore}, author={Shao, Qing and Hall, Carol K.}, year={2016}, pages={1–20} }
 @article{shao_hall_2016, title={Binding Preferences of Amino Acids for Gold Nanoparticles: A Molecular Simulation Study}, volume={32}, ISSN={["0743-7463"]}, DOI={10.1021/acs.langmuir.6b01693}, abstractNote={A better understanding of the binding preference of amino acids for gold nanoparticles of different diameters could aid in the design of peptides that bind specifically to nanoparticles of a given diameter. Here we identify the binding preference of 19 natural amino acids for three gold nanoparticles with diameters of 1.0, 2.0, and 4.0 nm, and investigate the mechanisms that govern these preferences. We calculate potentials of mean force between 36 entities (19 amino acids and 17 side chains) and the three gold nanoparticles in explicit water using well-tempered metadynamics simulations. Comparing these potentials of mean force determines the amino acids' nanoparticle binding preferences and if these preferences are controlled by the backbone, the side chain, or both. Twelve amino acids prefer to bind to the 4.0 nm gold nanoparticle, and seven prefer to bind to the 2.0 nm one. We also use atomistic molecular dynamics simulations to investigate how water molecules near the nanoparticle influence the binding of the amino acids. The solvation shells of the larger nanoparticles have higher water densities than those of the smaller nanoparticles while the orientation distributions of the water molecules in the shells of all three nanoparticles are similar. The nanoparticle preferences of the amino acids depend on whether their binding free energy is determined mainly by their ability to replace or to reorient water molecules in the nanoparticle solvation shell. The amino acids whose binding free energy depends mainly on the replacement of water molecules are likely to prefer to bind to the largest nanoparticle and tend to have relatively simple side chain structures. Those whose binding free energy depends mainly on their ability to reorient water molecules prefer a smaller nanoparticle and tend to have more complex side chain structures.}, number={31}, journal={LANGMUIR}, author={Shao, Qing and Hall, Carol K.}, year={2016}, month={Aug}, pages={7888–7896} }
 @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} }
 @article{shao_hall_2016, title={Protein adsorption on nanoparticles: model development using computer simulation}, volume={28}, ISSN={["1361-648X"]}, DOI={10.1088/0953-8984/28/41/414019}, abstractNote={The adsorption of proteins on nanoparticles results in the formation of the protein corona, the composition of which determines how nanoparticles influence their biological surroundings. We seek to better understand corona formation by developing models that describe protein adsorption on nanoparticles using computer simulation results as data. Using a coarse-grained protein model, discontinuous molecular dynamics simulations are conducted to investigate the adsorption of two small proteins (Trp-cage and WW domain) on a model nanoparticle of diameter 10.0 nm at protein concentrations ranging from 0.5 to 5 mM. The resulting adsorption isotherms are well described by the Langmuir, Freundlich, Temkin and Kiselev models, but not by the Elovich, Fowler–Guggenheim and Hill–de Boer models. We also try to develop a generalized model that can describe protein adsorption equilibrium on nanoparticles of different diameters in terms of dimensionless size parameters. The simulation results for three proteins (Trp-cage, WW domain, and GB3) on four nanoparticles (diameter  =  5.0, 10.0, 15.0, and 20.0 nm) illustrate both the promise and the challenge associated with developing generalized models of protein adsorption on nanoparticles.}, number={41}, journal={JOURNAL OF PHYSICS-CONDENSED MATTER}, author={Shao, Qing and Hall, Carol K.}, year={2016}, month={Oct} }