Biochemistry, Biophysics, and Structural Biology Commons^™

Computational Investigation Of The Pore Formation Mechanism Of Beta-Hairpin Antimicrobial Peptides, Richard Lipkin

Dissertations, Theses, and Capstone Projects

β-hairpin antimicrobial peptides (AMPs) are small, usually cationic peptides that provide innate biological defenses against multiple agents. They have been proposed as the basis for novel antibiotics, but their pore formation has not been directly observed on a molecular level. We review previous computational studies of peptide-induced membrane pore formation and report several new molecular dynamics simulations of β-hairpin AMPs to elucidate their pore formation mechanism. We simulated β-barrels of various AMPs in anionic implicit membranes, finding that most of the AMPs’ β-barrels were not as stable as those of protegrin. We also performed an optimization study of protegrin β-barrels …

Insight Into The Interaction Between The Peroxisome Proliferator-Activated Receptor Gamma (Pparγ) And Adipocyte Fatty Acid-Binding Protein (A-Fabp), Qian Wang

Dissertations, Theses, and Capstone Projects

The Adipocyte Fatty Acid-Binding Protein (AFABP) is mainly expressed in fat cells. It can bind fatty acids and other lipophilic substances such as eicosanoids and retinoids. The peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor protein that requires ligand binding to regulate the specific gene transcription. PPARγ is expressed at extremely high levels in adipose tissue, macrophages, and the large intestine, where it controls lipid adipogenesis and energy conversion. Moreover, it has been found that AFABP and PPARγ can form a complex in vivo. It is proposed that AFABP carries the ligand and enters into the nucleus where it …

Chloride And Proton Binding In The E. Coli 2cl¯:1h+ Clc Exchanger, Catherine Chenal

Dissertations, Theses, and Capstone Projects

The CLC family of membrane proteins is a ubiquitously expressed class of proton and usually voltage-activated chloride transporters involved in a myriad of physiological functions. Crystallographic structures identify up to three chloride binding sites: external, central and intracellular located in the inner half of the trans-membrane domain. The CLC proteins, except for the kidney isoforms, are gated by the extracellular side-facing gating Glutamate (Ex, E148 in CLC-ec1, the E. coli exchanger), which is thought to undergo a conformational change upon protonation.

To sort out how the thermodynamic paths to H+ coupled Cl¯ binding and conformational change in CLC-ec1 at the …