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Since the identification of the CF gene, less than 3 years ago, progress in analysing the function of its product, the cystic fibrosis transmembrane conductance regulator (CFTR), has been remarkable. It is now clear that CFTR functions as a small conductance chloride channel in epithelial membranes. However, many other questions remain unanswered. How does(More)
The free energy of partitioning an amino acid side chain from water into the cell membrane is one of the critical parameters for understanding and predicting membrane protein stability, and understanding membrane protein function. Transmembrane segments are generally very hydrophobic, but may contain hydrophilic residues that are important for the structure(More)
We calculated the free energy of solvation of the neutral analogs of 18 amino acid side-chains (not including glycine and proline) using the OPLS all-atom force field in TIP4P water, SPC water, and cyclohexane by molecular dynamics simulation and thermodynamic integration. The average unsigned errors in the free energies of solvation in TIP4P, SPC, and(More)
We present an extension of the coarse-grained MARTINI model for proteins and apply this extension to amyloid-and elastin-like peptides. Atomistic simulations of tetrapeptides, octapeptides, and longer peptides in solution are used as a reference to parametrize a set of pseudodihedral potentials that describe the internal flexibility of MARTINI peptides. We(More)
Molecular dynamics simulations of the RN24 peptide, which includes a diverse set of structurally heterogeneous states, are carried out in explicit solvent. Two approaches are employed and compared directly under identical simulation conditions. Specifically, we examine sampling by two individual long trajectories (microsecond timescale) and many shorter(More)
Reversible electropermeabilization (electroporation) is widely used to facilitate the introduction of genetic material and pharmaceutical agents into living cells. Although considerable knowledge has been gained from the study of real and simulated model membranes in electric fields, efforts to optimize electroporation protocols are limited by a lack of(More)
Computer simulations offer a valuable way to study membrane systems, from simple lipid bilayers to large transmembrane protein complexes and lipid-nucleic acid complexes for drug delivery. Their accuracy depends on the quality of the force field parameters used to describe the components of a particular system. We have implemented the widely used CHARMM22(More)
  • Alex K. K. Leung, Ismail M. Hafez, Svetlana Baoukina, Nathan M. Belliveau, Igor V. Zhigaltsev, Elham Afshinmanesh +4 others
  • 2012
Lipid nanoparticles (LNP) containing ionizable cationic lipids are the leading systems for enabling therapeutic applications of siRNA; however, the structure of these systems has not been defined. Here we examine the structure of LNP siRNA systems containing DLinKC2-DMA(an ionizable cationic lipid), phospholipid, cholesterol and a polyethylene glycol (PEG)(More)
Nosocomial infections with Enterococcus faecalis are an emerging health problem. However, drug efflux pumps contributing to intrinsic drug resistance are poorly studied in this Gram-positive pathogen. In this study, we functionally investigated seven heterodimeric ABC transporters of E. faecalis that are annotated as drug efflux pumps. Deletion of(More)