This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Recent experimental studies have shown that various degenerative diseases are associated with deposition in the body tissues of insoluble protein aggregates that have a particular (3-sheet conformation. These aggregates have been termed amyloidal fibrils. It has been proposed that the formation of amyloidal fibrils is determined by the nature of the intermediate unfolding species. Moreover, recent experimental studies have shown that amyloidal fibril formation might be favor when proteins are confined in membranes. However, not enough theoretical or experimental considerations have been focused on elucidate the extend of the effect and/or role that membranes plays in the amyloidal fibril formation. This becomes an important issue to address since polymeric protein delivery systems provide a suitable environment for protein fibrillization to occur. We propose to develop state-of-the-art computer simulations and experimental techniques to study the formation of the amyloidal fibrils under a series of well-defined and biologically relevant conditions. Specifically, coarse-grained and all-atom potentials will be used and/or develop to properly describe the interparticle forces. Monte Carlo and Molecular Dynamic simulations will be coupled to appropriate sampling techniques to determine the structure and stability of the aggregates. Experimental techniques will be designed and implemented to characterize the extend to which a given peptide will eventually form fibrils or amorphous aggregates. The results are expected to uncover basic trends (such as amino acid sequence, charge, ad hydrophobicity) on the molecular description of amyloidal fibril formations. These basic trends will permit the development of prediction capabilities for the possible fibril formation given the system (protein structure) and the experimental set-up (solvent, ionic strength, thermodynamic state, and presence of a membrane). By recognizing membrane compliance as an important additional consideration, we expect to deepen our understanding of the role of membrane composition and interface as a possible controller of fibrilar formation. Examples of these systems are insulin, lysozime, myoglobin, and STVIIE. Polymeric membranes of various composition, that provide a range of polarities, will be used.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR016470-11
Application #
8360155
Study Section
Special Emphasis Panel (ZRR1-RI-4 (01))
Project Start
2011-06-01
Project End
2012-05-31
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
11
Fiscal Year
2011
Total Cost
$102,020
Indirect Cost
Name
University of Puerto Rico Rio Piedras
Department
Type
DUNS #
090051616
City
San Juan
State
PR
Country
United States
Zip Code
00926
Cantres-Rosario, Yisel M; Acevedo-Mariani, Frances M; Pérez-Laspiur, Juliana et al. (2017) Microwave & magnetic proteomics of macrophages from patients with HIV-associated cognitive impairment. PLoS One 12:e0181779
Mariño, Yobana A; Verle Rodrigues, José C; Bayman, Paul (2017) Wolbachia Affects Reproduction and Population Dynamics of the Coffee Berry Borer (Hypothenemus hampei): Implications for Biological Control. Insects 8:
Martínez-Rivera, Freddyson J; Pérez-Laspiur, Juliana; Santiago-Gascot, María E et al. (2017) Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids. PLoS One 12:e0180409
Zenón, Frances; Jorge, Inmaculada; Cruz, Ailed et al. (2016) 18O proteomics reveal increased human apolipoprotein CIII in Hispanic HIV-1+ women with HAART that use cocaine. Proteomics Clin Appl 10:144-55
Rivera-Rivera, Yainyrette; Vázquez-Santiago, Fabián J; Albino, Elinette et al. (2016) Impact of Depression and Inflammation on the Progression of HIV Disease. J Clin Cell Immunol 7:
Martínez-Rivera, Freddyson J; Rodriguez-Romaguera, Jose; Lloret-Torres, Mario E et al. (2016) Bidirectional Modulation of Extinction of Drug Seeking by Deep Brain Stimulation of the Ventral Striatum. Biol Psychiatry 80:682-690
Suárez-Arroyo, Ivette J; Rios-Fuller, Tiffany J; Feliz-Mosquea, Yismeilin R et al. (2016) Ganoderma lucidum Combined with the EGFR Tyrosine Kinase Inhibitor, Erlotinib Synergize to Reduce Inflammatory Breast Cancer Progression. J Cancer 7:500-11
Suárez-Arroyo, Ivette J; Feliz-Mosquea, Yismeilin R; Pérez-Laspiur, Juliana et al. (2016) The proteome signature of the inflammatory breast cancer plasma membrane identifies novel molecular markers of disease. Am J Cancer Res 6:1720-40
Wang, Hai-Yang; Huang, Kun; De Jesús, Melvin et al. (2016) Synthesis of enantiopure 1,2-azido and 1,2-amino alcohols via regio- and stereoselective ring-opening of enantiopure epoxides by sodium azide in hot water. Tetrahedron Asymmetry 27:91-100
Colon, Krystal; Perez-Laspiur, Juliana; Quiles, Raymond et al. (2016) Macrophage secretome from women with HIV-associated neurocognitive disorders. Proteomics Clin Appl 10:136-43

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