Michael Klein

In all-atom simulations of lipid membranes, explicit hydrogen atoms contained in the hydrocarbon region are described by a large number of degrees of freedom, although they convey only limited physical information. We propose an implicit-hydrogen model for saturated and monounsaturated acyl chains, aimed at complementing the all-atom CHARMM27 model for phospholipid headgroups. Torsional potentials and nonbonded parameters were fitted to reproduce experimental data and free energy surfaces of all-atom model systems. Comparative simulations of fluid-phase POPC bilayers were performed using the all-hydrogen force field and the present model. The hybrid model accelerates a typical bilayer simulation by about 50% while sacrificing a minimal amount of detail with respect to the fully atomistic description. In addition, the united-atom description is energetically compatible with all-atom CHARMM models, making it suitable for simulations of complex membrane systems.

Phospholipid membranes play a key role in compartmentalization, as a medium for other species such as proteins to function, and as a structural scaffolding for cells. Recently interest is focusing on more active roles of phospholipids in the affecting the behavior of membrane proteins, ...

A series of first principles molecular dynamics and Monte Carlo simulations were carried out for liquid water to investigate the reproducibility of different sampling approaches. These simulations include Car−Parrinello molecular dynamics simulations using the program cpmd with ...

The structure of linear water wires with an excess proton was studied at room temperature using ab initio path integral molecular dynamics. The ab initio Car-Parrinello (CP) methodology employed the density functional theory (DFT) description of the electronic ...

Dinuclear azole-bridged Pt compounds bind to DNA helices, forming intrastrand crosslinks between adjacent guanines in a similar way to cisplatin. Their cytotoxic profile is, however, different from that of first and second generation Pt drugs in that they lack cross resistance in cisplatin-resistant cell lines. In contrast to cisplatin, which induces a large kink in DNA duplex, structural NMR studies and molecular dynamics simulations have shown that azole-bridged diplatinum compounds induce only small structural changes in double-stranded DNA. These structural differences have been invoked to explain the different cytotoxic profile of these compounds. Here, we show that in addition to the small structural changes in DNA, dinuclear Pt compounds also affect DNA minor groove flexibility in a different way than cisplatin. Free-energy calculations on azole-bridged diplatinum DNA adducts reveal that opening of the minor groove requires a higher free-energy cost (DeltaG ~ 7-15 kcal/mol) than in the corresponding cisplatin-DNA adduct (DeltaG ~ 0 kcal/mol). This could prevent minor groove binding proteins from binding to diplatinum-DNA adducts thus leading to a different cellular response than cisplatin and possibly decreasing the activity of excision repair enzymes. Although the development of drug resistance is a highly complex mechanism, our findings provide an additional rationale for the improved cytotoxic activity of these compounds in cell lines resistant to cisplatin.

Combining single-walled carbon nanotubes (CNT) with biological molecules provides a route to novel nanoscale materials with many promising applications in nanotechnology and nanomedicine. Recent experiments show that CNTs covalently functionalized with the coxsackie-adenovirus receptor (CAR) serve as biosensors capable of specifically recognizing Knob proteins from the adenovirus capsid. These experiments suggest that CAR retains its biologically active form when bound to CNT, but a detailed understanding of the structural changes that occur within CAR after CNT attachment is lacking. To address this, we have performed all-atom classical molecular dynamics (MD) simulations of CAR and the CAR-Knob complex in aqueous solution alone and also when covalently linked to CNT. The MD results show that the CNT damps structural fluctuations in CAR and reduces the internal mobility of the protein. However, CNT induces very little structural deformation and does not affect CAR's ability to specifically bind Knob. This MD study verifies that CAR retains its biological functionality when attached to CNT and provides a computational approach to rationalize nanobiosensing devices.

Molecular dynamics (MD) simulations have been carried out to investigate the morphology of monolayers of the cationic surfactant cetyltrimethylammonium bromide (C16TAB) at the interface between a hydrophobic substrate and an aqueous solution. The simulation ...

Polymersomes are self-assembled shells of amphiphilic block copolymers that are currently being developed by many groups for fundamental insights into the nature of self-assembled states as well as for a variety of potential applications. While recent reviews have highlighted distinctive properties - particularly stability - that are strongly influenced by both copolymer type and polymer molecular weight, here we first review some of the more recent developments in computational molecular dynamics (MD) schemes that lend insight into assembly. We then review polymersome loading, in vivo stealthiness, degradation-based disassembly for controlled release, and even tumor-shrinkage in vivo. Comparisons of polymersomes with viral capsids are shown to encompass and inspire many aspects of current designs.

The results of first-principles electronic structure calculations are reported for the molecule Li(NH3)4 and the metallic molecular crystal of the same composition. We show how spatially extended valence states of the molecules combine to yield a conduction band in the crystal. The electronic density associated with conduction states percolates along winding channels; the H atoms appear to play a key

ABSTRACT Molecular-dynamics calculations have been used to investigate the nature of critical fluctuations in the paraelectric phase of NaN${\mathrm{O}}_{2}$. Although the ${(\mathrm{N}{\mathrm{O}}_{2})}^{$-${}}$ anions are found to reorient rapidly, predominantly about the crystal $c$ axis, the simulation reveals the existence of long-lived fluctuations of antiferroelectric character. The reorientational motion is found to couple to optic rather than acoustic modes, in agreement with a recent theoretical prediction.