Scaling and Alpha-Helix Regulation of Protein Relaxation in a Lipid Bilayer

Protein conformation and orientation in the lipid membrane plays a key role in many cellular processes. Here we use molecular dynamics simulation to investigate the relaxation and C-terminus diffusion of a model helical peptide: beta-amyloid (Aβ) in a lipid membrane.We observed that after the helical peptide was initially half-embedded in the extracelluar leaflet of phosphatidylcholine (PC) or PC/cholesterol (PC/CHOL) membrane, the C-terminus diffused across the membrane and anchored to PC headgroups of the cytofacial lipid leaflet. In some cases, the membrane insertion domain of the Aβ was observed to partially unfold. Applying a sigmoidal fit to the process, we found that the characteristic velocity of the C-terminus, as it moved to its anchor site, scaled with θu −4/3, where θu is the fraction of the original helix that was lost during a helix to coil transition. Comparing this scaling with that of bead-spring models of polymer relaxation suggests that the C-terminus velocity is highly regulated by the peptide helical content, but that it is independent of the amino acid type. The Aβ was stabilized by the attachment of the positive Lys28 side chain to the negative phosphate of PC or 3β oxygen of CHOL in the extracellular lipid leaflet and of the C-terminus to its anchor site in the cytofacial lipid leaflet

Molecular Dynamics Simulations Reveal the Protective Role of Cholesterol in β-Amyloid Protein-Induced Membrane Disruptions in Neuronal Membrane Mimics

Interactions of β-amyloid (Aβ) peptides with neuronal membranes have been associated with the pathogenesis of Alzheimer\u27s disease (AD); however, the molecular details remain unclear. We used atomistic molecular dynamics (MD) simulations to study the interactions of Aβ40 and Aβ42 with model neuronal membranes. The differences between cholesterol-enriched and depleted lipid domains were investigated by the use of model phosphatidylcholine (PC) lipid bilayers with and without 40 mol % cholesterol. A total of 16 independent 200 ns simulation replicates were investigated. The surface area per lipid, bilayer thickness, water permeability barrier, and lipid order parameter, which are sensitive indicators of membrane disruption, were significantly altered by the inserted state of the protein. We conclude that cholesterol protects Aβ-induced membrane disruption and inhibits β-sheet formation of Aβ on the lipid bilayer. The latter could represent a two-dimensional (2D) seeding template for the formation of toxic oligomeric Aβ in the pathogenesis of AD

Data supporting beta-amyloid dimer structural transitions and protein–lipid interactions on asymmetric lipid bilayer surfaces using MD simulations on experimentally derived NMR protein structures

This data article supports the research article entitled “Maximally Asymmetric Transbilayer Distribution of Anionic Lipids Alters the Structure and interaction with Lipids of an Amyloidogenic Protein Dimer Bound to the Membrane Surface” [1]. We describe supporting data on the binding kinetics, time evolution of secondary structure, and residue-contact maps of a surface-absorbed beta-amyloid dimer protein on different membrane surfaces. We further demonstrate the sorting of annular and non-annular regions of the protein/lipid bilayer simulation systems, and the correlation of lipid-number mismatch and surface area per lipid mismatch of asymmetric lipid membranes. Keywords: Asymmetric lipid membranes, Protein structure on surfaces, Protein–lipid interactions, Protein aggregation, Beta-Amyloi

Defect-Dominated Doping and Contact Resistance in MoS₂

Achieving low resistance contacts is vital for the realization of nanoelectronic devices based on transition metal dichalcogenides. We find that intrinsic defects in MoS₂ dominate the metal/MoS₂ contact resistance and provide a low Schottky barrier independent of metal contact work function. Furthermore, we show that MoS₂ can exhibit both n-type and p-type conduction at different points on a same sample. We identify these regions independently by complementary characterization techniques and show how the Fermi level can shift by 1 eV over tens of nanometers in spatial resolution. We find that these variations in doping are defect-chemistry-related and are independent of contact metal. This raises questions on previous reports of metal-induced doping of MoS₂ since the same metal in contact with MoS₂ can exhibit both n- and p-type behavior. These results may provide a potential route for achieving low electron and hole Schottky barrier contacts with a single metal deposition

Comprehensive Capacitance-Voltage Simulation and Extraction Tool Including Quantum Effects for High-k on SixGe1-x and InxGa1-xAs: Part II-Fits and Extraction from Experimental Data

Capacitance-voltage (C-V) measurement and analysis is highly useful for determining important information about MOS gate stacks. Parameters such as the equivalent oxide thickness (EOT), substrate doping density, flatband voltage, fixed oxide charge, density of interface traps (Dit), and effective gate work function can all be extracted from experimental C-V curves. However, to extract these gate-stack parameters accurately, the correct models must be utilized. In Part I, we described the modeling and implementation of a C-V code that can be used for alternative channel semiconductors in conjunction with high-k gate dielectrics and metal gates. Importantly, this new code (CV ACE) includes the effects of nonparabolic bands and quantum capacitance, enabling accurate models to be applied to experimental C-V curves. In this paper, we demonstrate the capabilities of this new code to extract accurate parameters, including EOT and Dit profiles from experimental high-k on Ge and In0.53Ga0.47As gate stacks

Comprehensive Capacitance-Voltage Simulation and Extraction Tool Including Quantum Effects for High-k on SixGe1-x and InxGa1-xAs: Part I-Model Description and Validation

High-mobility alternative channel materials to silicon are critical to the continued scaling of MOS devices. The analysis of capacitance-voltage (C-V) measurements on these new materials with high-k gate dielectrics is a critical technique to determine many important gate-stack parameters. While there are very useful C-V analysis tools available to the community, these tools are all limited in their applicability to alternative semiconductor channel MOS gate-stack analysis since they were developed for silicon. Here, we report on a new comprehensive C-V simulation and extraction tool, called CV Alternative Channel Extraction (ACE), that incorporates a wide range of semiconductors and dielectrics with the capability to implement customized gate stacks. Fermi-Dirac carrier statistics, nonparabolic bands, and quantum mechanical effects are all implemented with options to turn each of these off as the user desires. Interface state capacitance (Cit) is implemented using a common model for systems like Si and Ge. A more complex Cit model is also implemented for III-Vs that accurately captures frequency dispersion in accumulation that arises from tunneling. CV ACE enables extremely fast simulation and extraction and can accommodate measurements performed at variable temperatures and frequencies to allow for a more accurate extraction of interface state density (Dit)

HfO₂ on MoS₂ by Atomic Layer Deposition: Adsorption Mechanisms and Thickness Scalability

We report our investigation of the atomic layer deposition (ALD) of HfO₂ on the MoS₂ surface. In contrast to previous reports of conformal growth on MoS₂ flakes, we find that ALD on MoS₂ bulk material is not uniform. No covalent bonding between the HfO₂ and MoS₂ is detected. We highlight that individual precursors do not permanently adsorb on the clean MoS₂ surface but that organic and solvent residues can dramatically change ALD nucleation behavior. We then posit that prior reports of conformal ALD deposition on MoS₂ flakes that had been exposed to such organics and solvents likely rely on contamination-mediated nucleation. These results highlight that surface functionalization will be required before controllable and low defect density high-κ/MoS₂ interfaces will be realized. The band structure of the HfO₂/MoS₂ system is experimentally derived with valence and conduction band offsets found to be 2.67 and 2.09 eV, respectively