Ionic Strength and Solution Composition Dictate the Adsorption of Cell-Penetrating Peptides onto Phosphatidylcholine Membranes.

Adsorption of arginine-rich positively charged peptides onto neutral zwitterionic phosphocholine (PC) bilayers is a key step in the translocation of those potent cell-penetrating peptides into the cell interior. In the past, we have shown both theoretically and experimentally that polyarginines adsorb to the neutral PC-supported lipid bilayers in contrast to polylysines. However, comparing our results with previous studies showed that the results often do not match even at the qualitative level.

Arginine-rich cell-penetrating peptides induce membrane multilamellarity and subsequently enter via formation of a fusion pore.

Arginine-rich cell-penetrating peptides do not enter cells by directly passing through a lipid membrane; they instead passively enter vesicles and live cells by inducing membrane multilamellarity and fusion. The molecular picture of this penetration mode, which differs qualitatively from the previously proposed direct mechanism, is provided by molecular dynamics simulations. The kinetics of vesicle agglomeration and fusion by an iconic cell-penetrating peptide-nonaarginine-are documented via real-time fluorescence techniques, while the induction of multilamellar phases in vesicles and live cells is demonstrated by a combination of electron and fluorescence microscopies.

Calcium ions in aqueous solutions: Accurate force field description aided by ab initio molecular dynamics and neutron scattering.

We present a combination of force field and ab initio molecular dynamics simulations together with neutron scattering experiments with isotopic substitution that aim at characterizing ion hydration and pairing in aqueous calcium chloride and formate/acetate solutions. Benchmarking against neutron scattering data on concentrated solutions together with ion pairing free energy profiles from ab initio molecular dynamics allows us to develop an accurate calcium force field which accounts in a mean-field way for electronic polarization effects via charge rescaling. This refined calcium parameterization is directly usable for standard molecular dynamics simulations of processes involving this key biological signaling ion.

Redox Potentials for Tetraplatin, Satraplatin, Its Derivatives, and Ascorbic Acid: A Computational Study.

Redox potentials of the Pt(IV) complexes, such as satraplatin, tetraplatin, and several others, are determined at the density functional theory (DFT) level (with B3LYP, ω-B97XD, PBE1PBE, TPSSTPSS, M06-L, M11-L, and MN12-L functionals) and compared with post-Hartree-Fock methods MP2 and CCSD(T). Calculations are performed in water solution employing an implicit solvation model. The impact of replacement of a chloro ligand by a water molecule (hydration in the equatorial plane of the complexes) is also explored.

Guanidinium Pairing Facilitates Membrane Translocation.

Ab initio free energy calculations of guanidinium pairing in aqueous solution confirm the counterintuitive conjecture that the like-charge ion pair is thermodynamically stable. Transferring the guanidinium pair to the inside of a POPC lipid bilayer, like-charge ion pairing is found to occur also inside the membrane defect. It is found to contribute to the nonadditivity of ion transfer, thereby facilitating the presence of ions inside the bilayer.