Bulletin of the American Physical Society
2017 Annual Meeting of the APS Mid-Atlantic Section
Volume 62, Number 19
Friday–Sunday, November 3–5, 2017; Newark, New Jersey
Session N1: Protein Aggregation |
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Chair: Luca Larini, Rutgers University, Camden Room: 235, Campus Center, NJIT |
Sunday, November 5, 2017 12:15PM - 12:51PM |
N1.00001: $\alpha -$synuclein aggregation and inhibition: the role of $\beta $-synuclein Invited Speaker: Jean Baum $\alpha -$synuclein ($\alpha $S) is a small neuronal intrinsically disordered protein (IDP) that self-associates to form oligomers and fibrils in the brains of patients with Parkinson's disease. The highly homologous protein $\beta $-synuclein ($\beta $S) co-localizes with $\alpha $S and can act as a neuro-protector of $\alpha $S toxicity \textit{in vivo }to inhibit pathological $\alpha $S aggregation. Using NMR and biophysical approaches, we will discuss the molecular mechanisms of $\alpha $S inhibition by $\beta $S and demonstrate the presence of an environmentally sensitive pH switch for $\beta $S that serves as an on/off fibrillation switch at mildly acidic physiological pH. These results have several implications for the role of $\beta $S in disease and highlight the complex interplay of $\alpha $S and $\beta $S in the cell. [Preview Abstract] |
Sunday, November 5, 2017 12:51PM - 1:03PM |
N1.00002: Surface Effects on the Dynamics of Confined Short Peptides: A Computational Study Luis Cruz In the cell, proteins perform their biological function by folding into their native state within confined spaces naturally provided by membranes and chaperones, among others. Of particular importance are proteins that do not have a native state, known as intrinsically disordered proteins (IDP), that exist mainly in random structures whose function is not well understood. Some of these IDPs, known to misfold and aggregate, have been associated with neurological diseases, such as the amyloid beta-protein (Abeta) in Alzheimer's disease. Here, results derived from molecular dynamics simulations will be presented that highlight the effects of different surfaces of confining pores on the dynamics of two fragments of the full-length Abeta, the Abeta(21-30) and Abeta(16-22) peptides. Simulations reveal that confinement in these nanometer-sized pores significantly change the dynamics of the peptides, and in particular, can stabilize transient structures by affecting the solvent within these pores. The degree of stability of structure will be shown to involve the delicate role of the confined solvent on mediating the peptide-surface interactions. Possible connections with amyloid formation and aggregation will be discussed. [Preview Abstract] |
Sunday, November 5, 2017 1:03PM - 1:15PM |
N1.00003: Thermodynamic stability of polar and non-polar amyloid fibrils Farbod Mahmoudinobar, Zhaoqian Su, Cristiano L. Dias Protein aggregation into fibril-like structures is the hallmark of amyloid diseases that included Alzheimer's, Parkinson's and type 2 diabetes. An understanding of the molecular forces driving fibril formation may provide insights into strategies to prevent these diseases. Thermodynamics has played an important role in unraveling the molecular mechanisms of different conformational changes in proteins, e.g., protein folding. However, equilibrium thermodynamic quantities of amyloid fibrils are not easily accessible experimentally and they remain largely unknown. In this work, we discuss results from all-atom molecular dynamics simulations in which we measured equilibrium thermodynamic quantities related to addition/dissociation of a peptide to/from a fibril. We will highlight differences in the thermodynamic properties of polar and non-polar fibrils. Simulations were performed using an umbrella sampling protocol combined with replica exchange molecular dynamics to compute potential of mean force (PMF) of peptide addition as a function of temperature. The temperature dependence of the PMF is used to compute changes in entropy, enthalpy and heat capacity of peptide addition. We find that the non-polar fibril becomes more stable with increasing temperature and its stability is dominated by entropy. In contrast, the polar fibril becomes less stable with increasing temperature while it is stabilized by enthalpy. These behaviors are consistent with the nature of the interactions in their dry core and they highlight the importance of side chains accounting for stability of amyloid fibrils. [Preview Abstract] |
Sunday, November 5, 2017 1:15PM - 1:27PM |
N1.00004: Wavelength-specific, plasmonic nanoparticle mediated rupture of polymersomes using ultrafast single-pulse irradiation Julianne Griepenburg, Abby Robinson, Gina DiSalvo, Sean O'Malley, Daniel Bubb Polymersomes are robust vesicles that are self-assembled from amphiphilic diblock copolymers. They are of tremendous interest in the field of drug delivery due to their ability to stably encapsulate molecules within both the hydrophobic membrane and hydrophilic lumen of the vesicle. In this study, light-stimulated release of hydrophilic encapsulants has been achieved through the incorporation of plasmonic nanoparticles, facilitating disruption of the membrane upon ultrafast, single-pulse irradiation. Cargo release can be controlled ranging from complete vesicle rupture and instantaneous release, to membrane pore formation and effusion. Single vesicle release kinetics were found by monitoring temporal fluorescence intensity from an individual vesicle and determined to be related to pulse energy and nanoparticle location. [Preview Abstract] |
Sunday, November 5, 2017 1:27PM - 2:03PM |
N1.00005: Insights into Cross-Linked Amyloid $\beta$-Protein Oligomers and Their Role in Alzheimer's Disease Invited Speaker: Brigita Urbanc Protein misfolding and aberrant protein aggregation are at the core of many age--triggered diseases, such as Alzheimer's, Parkinson's, and Huntington's disease, amyotrophic lateral sclerosis, type II diabetes, systemic amyloidoses, and others. Proteins associated with these diseases do not share any obvious aspects of the primary structure yet they self--assemble into cytotoxic low--molecular weight oligomers and form fibrils with a common cross-$\beta$ structure. Amyloid $\beta$-protein (A$\beta$) assembly plays a central role in Alzheimer's disease (AD), which is the leading cause of dementia in elderly worldwide. I will describe several computational and experimental approaches that offer insights into formation of A$\beta$ oligomers under oxidative stress conditions occurring in aging brain, which may stabilize A$\beta$ oligomers, inhibit their structural conversion into amyloid fibrils, and prolong their toxic action. Formation and structure of cross-linked A$\beta$ oligomers may hold a key to understanding the basis of A$\beta$ oligomer toxicity and provide clues on how to inhibit their toxic action. [Preview Abstract] |
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