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Amyloid fibrils represent a stable form of many misfolded proteins associated with numerous diseases. Among these are Parkinson's disease (alpha-synuclein), Type II diabetes (islet amyloid polypeptide), and Alzheimer's disease (amyloid beta-peptide, Abeta). The appearance of Abeta fibrils in neural tissue is a hallmark of Alzheimer's disease, and many(More)
GridMAT-MD is a new program developed to aid in the analysis of lipid bilayers from molecular dynamics simulations. It reads a GROMACS coordinate file and generates two types of data: a two-dimensional contour plot depicting membrane thickness, and a polygon-based tessellation of the individual lipid headgroups. GridMAT-MD can also account for proteins or(More)
Proper treatment of nonbonded interactions is essential for the accuracy of molecular dynamics (MD) simulations, especially in studies of lipid bilayers. The use of the CHARMM36 force field (C36 FF) in different MD simulation programs can result in disagreements with published simulations performed with CHARMM due to differences in the protocols used to(More)
The amyloid β-peptide (Aβ) is a 40-42 residue peptide that is the principal toxic species in Alzheimer's disease (AD). The oxidation of methionine-35 (Met35) to the sulfoxide form (Met35(ox)) has been identified as potential modulator of Aβ aggregation. The role Met35(ox) plays in Aβ neurotoxicity differs among experimental studies, which may be due to(More)
The pathogenic aggregation of the amyloid β-peptide (Aβ) is considered a hallmark of the progression of Alzheimer's disease, the leading cause of senile dementia in the elderly and one of the principal causes of death in the United States. In the absence of effective therapeutics, the incidence and economic burden associated with the disease are expected to(More)
Alzheimer's disease is a progressive, neurodegenerative disorder that is the leading cause of senile dementia, afflicting millions of individuals worldwide. Since the identification of the amyloid beta-peptide (Abeta) as the principal toxic entity in the progression of Alzheimer's disease, numerous attempts have been made to reduce endogenous Abeta(More)
Tyrosine aminotransferase (TAT) catalyzes the transamination of tyrosine and other aromatic amino acids. The enzyme is thought to play a role in tyrosinemia type II, hepatitis and hepatic carcinoma recovery. The objective of this study is to investigate its biochemical and structural characteristics and substrate specificity in order to provide insight(More)
Molecular dynamics simulations are being applied to increasingly complex systems, including those involving small endogenous compounds and drug molecules. In order to obtain meaningful and accurate data from these simulations, high-quality topologies for small molecules must be generated in a manner that is consistent with the derivation of the force field(More)
Peroxisome-proliferator activated receptor-γ (PPARγ) is a nuclear hormone receptor that forms a heterodimeric complex with retinoid X receptor-α (RXRα) to regulate transcription of genes involved in fatty acid storage and glucose metabolism. PPARγ is a target for pharmaceutical intervention in type 2 diabetes, and insight into interactions between PPARγ,(More)
The etiology of Alzheimer's disease is considered to be linked to interactions between amyloid beta-peptide (Abeta) and neural cell membranes. Membrane disruption and increased ion conductance have been observed in vitro in the presence of Abeta, and it is assumed that these same phenomena occur in the brain of an individual afflicted with Alzheimer's. The(More)