@article{marchut_hall_2007, title={Effects of chain length on the aggregation of model polyglutamine peptides: Molecular dynamics simulations}, volume={66}, ISSN={["0887-3585"]}, DOI={10.1002/prot.21132}, abstractNote={Aggregation in the brain of polyglutamine-containing proteins is either a cause or an associated symptom of nine hereditary neurodegenerative disorders including Huntington's disease. The molecular level mechanisms by which these proteins aggregate are still unclear. In an effort to shed light on this important phenomenon, we are investigating the aggregation of model polyglutamine peptides using molecular-level computer simulation with a simplified model of polyglutamine that we have developed. This model accounts for the most important types of intra- and inter-molecular interactions-hydrogen bonding and hydrophobic interactions-while allowing the folding process to be simulated in a reasonable time frame. The model is used to examine the folding of isolated polyglutamine peptides 16, 32, and 48 residues long and the folding and aggregation of systems of 24 model polyglutamine peptides 16, 24, 32, 36, 40, and 48 residues long. Although the isolated polyglutamine peptides did form some alpha and beta backbone-backbone hydrogen bonds they did not have as many of these bonds as they would have if they had folded into a complete alpha helix or beta sheet. In one of the simulations on the isolated polyglutamine peptide 48 residues long, we observed a structure that resembles a beta helix. In the multi-chain simulations we observed amorphous aggregates at low temperatures, ordered aggregates with significant beta sheet character at intermediate temperatures, and random coils at high temperatures. We have found that the temperature at which the model peptides undergo the transition from amorphous aggregates to ordered aggregates and the temperature at which the model peptides undergo the transition from ordered aggregates to random coils increase with increasing chain length. Our finding that the stability of the ordered aggregates increases as the peptide chain length increases may help to explain the experimentally observed relation between polyglutamine tract length and aggregation in vitro and disease progression in vivo. We have also observed in our simulations that the optimal temperature for the formation of beta sheets increases with chain length up to 36 glutamine residues but not beyond. Equivalently, at fixed temperature we find a transition from a region dominated by random coils at chain lengths less than 36 to a region dominated by relatively ordered beta sheet structures at chain lengths greater than 36. Our finding of this critical chain length of 36 glutamine residues is interesting because a critical chain length of 37 glutamine residues has been observed experimentally.}, number={1}, journal={PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS}, author={Marchut, Alexander J. and Hall, Carol K.}, year={2007}, month={Jan}, pages={96–109} }
 @article{marchut_smith_hall_2006, title={Commentary on: "Assembly of a tetrameric alpha-helical bundle: Computer simulations on an intermediate-resolution protein model" [Proteins 2001;44 : 376-391]}, volume={63}, ISSN={["1097-0134"]}, DOI={10.1002/prot.20896}, number={3}, journal={PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS}, author={Marchut, AJ and Smith, AV and Hall, CK}, year={2006}, month={May}, pages={709–710} }
 @article{marchut_hall_2006, title={Side-chain interactions determine amyloid formation by model polyglutamine peptides in molecular dynamics simulations}, volume={90}, ISSN={["1542-0086"]}, DOI={10.1529/biophysj.105.079269}, abstractNote={The pathological manifestation of nine hereditary neurodegenerative diseases is the presence within the brain of aggregates of disease-specific proteins that contain polyglutamine tracts longer than a critical length. To improve our understanding of the processes by which polyglutamine-containing proteins misfold and aggregate, we have conducted molecular dynamics simulations of the aggregation of model polyglutamine peptides. This work was accomplished by extending the PRIME model to polyglutamine. PRIME is an off-lattice, unbiased, intermediate-resolution protein model based on an amino acid representation of between three and seven united atoms, depending on the residue being modeled. The effects of hydrophobicity on the system are studied by varying the strength of the hydrophobic interaction from 12.5% to 5% of the hydrogen-bonding interaction strength. In our simulations, we observe the spontaneous formation of aggregates and annular structures that are made up of beta-sheets starting from random configurations of random coils. This result was interesting because tubular protofibrils were recently found in experiments on polyglutamine aggregation and because of Perutz's prediction that polyglutamine would form water-filled nanotubes.}, number={12}, journal={BIOPHYSICAL JOURNAL}, author={Marchut, Alexander J. and Hall, Carol K.}, year={2006}, month={Jun}, pages={4574–4584} }
 @article{marchut_hall_2006, title={Spontaneous formation of annular structures observed in molecular dynamics simulations of polyglutamine peptides}, volume={30}, ISSN={["1476-928X"]}, DOI={10.1016/j.compbiolchem.2006.01.003}, abstractNote={Annular structures have been observed experimentally in aggregates of polyglutamine-containing proteins and other proteins associated with diseases of the brain. Here we report the observation of annular structures in molecular-level simulations of large systems of model polyglutamine peptides. A system of 24 polyglutamine chains 16 residues long at a concentration of 5 mM spontaneously formed large beta sheets which curved to form tube-like annular structures that resemble beta barrels. This work was accomplished by extending the PRIME model to polyglutamine. PRIME is an off-lattice, unbiased, intermediate-resolution protein model based on an amino acid representation of between three and seven united atoms depending on the residue being modeled. Our results are interesting not only because of the recent discovery of tubular protofibrils in experiments on aggregation of mutant huntingtin fragments containing expanded polyglutamine tracts but also because Perutz predicted that polyglutamine forms water filled nanotubes.}, number={3}, journal={COMPUTATIONAL BIOLOGY AND CHEMISTRY}, author={Marchut, Alexander J. and Hall, Carol K.}, year={2006}, month={Jun}, pages={215–218} }
 @article{nguyen_marchut_hall_2004, title={Solvent effects on the conformational transition of a model polyalanine peptide}, volume={13}, ISSN={0961-8368}, url={http://dx.doi.org/10.1110/ps.04701304}, DOI={10.1110/ps.04701304}, abstractNote={Protein ScienceVolume 13, Issue 11 p. 2909-2924 ARTICLEFree Access Solvent effects on the conformational transition of a model polyalanine peptide Hung D. Nguyen, Hung D. Nguyen Department of Chemical Engineering, North Carolina State University, Raleigh, North Carolina 27695-7905, USASearch for more papers by this authorAlexander J. Marchut, Alexander J. Marchut Department of Chemical Engineering, North Carolina State University, Raleigh, North Carolina 27695-7905, USASearch for more papers by this authorCarol K. Hall, Corresponding Author Carol K. Hall hall@turbo.che.ncsu.edu Department of Chemical Engineering, North Carolina State University, Raleigh, North Carolina 27695-7905, USADepartment of Chemical Engineering, North Carolina State University, Raleigh, NC 27695-7905, USA; fax: (919) 515-3465.Search for more papers by this author Hung D. Nguyen, Hung D. Nguyen Department of Chemical Engineering, North Carolina State University, Raleigh, North Carolina 27695-7905, USASearch for more papers by this authorAlexander J. Marchut, Alexander J. Marchut Department of Chemical Engineering, North Carolina State University, Raleigh, North Carolina 27695-7905, USASearch for more papers by this authorCarol K. Hall, Corresponding Author Carol K. Hall hall@turbo.che.ncsu.edu Department of Chemical Engineering, North Carolina State University, Raleigh, North Carolina 27695-7905, USADepartment of Chemical Engineering, North Carolina State University, Raleigh, NC 27695-7905, USA; fax: (919) 515-3465.Search for more papers by this author First published: 29 December 2008 https://doi.org/10.1110/ps.04701304Citations: 76AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume13, Issue11November 2004Pages 2909-2924 FiguresReferencesRelatedInformation}, number={11}, journal={Protein Science}, publisher={Wiley}, author={Nguyen, Hung D. and Marchut, Alexander J. and Hall, Carol K.}, year={2004}, month={Dec}, pages={2909–2924} }