Biomedical subjects

Jan-Willem Handgraaf

Publications and source records attributed to Jan-Willem Handgraaf.

4 recordsLinked to original sources

PubMed2006

Two-dimensional ordered beta-sheet lipopeptide monolayers.

A series of amphiphilic lipopeptides, ALPs, consisting of an alternating hydrophilic and hydrophobic amino acid residue sequence coupled to a phospholipid tail, was designed to form supramolecular assemblies composed of beta-sheet monolayers decorated by lipid tails at the air-water interface. A straightforward synthetic approach based on solid-phase synthesis, followed by an efficient purification protocol was used to prepare the lipid-peptide conjugates. Structural insight into the organization of monolayers was provided by surface pressure versus area isotherms, circular dichroism, Fourier transform infrared spectroscopy, and Brewster angle microscopy. In situ grazing-incidence X-ray diffraction (GIXD) revealed that lipopeptides six to eight amino acids in length form a new type of 2D self-organized monolayers that exhibit beta-sheet ribbons segregated by lipid tails. The conclusions drawn from the experimental findings were supported by a representative model based on molecular dynamics simulations of amphiphilic lipopeptides at the vacuum-water interface.

Air↗

PubMed2006

Molecular dynamics study of onset of water gelation around the collagen triple helix.

The onset of water gelation around a collagen-like triple helix peptide was studied at ambient temperature and pressure by performing Molecular Dynamics simulations. The radial distribution functions of the oxygen and hydrogen atoms of water are distorted below 4 A from the peptide. The distortion is accompanied by the breakdown of the tetrahedral coordination of the hydrogen-bonded network of water molecules. The water shell around the peptide consists of alternating regions of higher and lower density. In agreement with experiments we find that the first hydration shell is kinetically labile, with a residence time in the order of picoseconds for a water molecule. From the computed diffusion coefficient, a key measure of the collective dynamics, we estimate the average diffusion speed decreases by a factor of 1.5 close to the peptide compared to the liquid. Our results give new insight in gel formation and structure on a molecular level.

Collagen↗

PubMed2004

Density-functional theory-based molecular simulation study of liquid methanol.

We present a density-functional theory based molecular dynamics study of the structural, dynamical, and electronic properties of liquid methanol under ambient conditions. The calculated radial distribution functions involving the oxygen and hydroxyl hydrogen show a pronounced hydrogen bonding and compare well with recent neutron diffraction data. We observe that, in line with infrared spectroscopic data, the hydroxyl-stretching mode is significantly redshifted in the liquid, whereas the hydroxyl bending mode shows a blueshift. A substantial enhancement of the molecular dipole moment is accompanied by significant fluctuations due to thermal motion. We compute a value of 32 for the relative permittivity, almost identical to the experimental value of 33. Our results provide valuable data for improvement of empirical potentials.

Journal Article↗

PubMed2004

Voronoi deformation density (VDD) charges: Assessment of the Mulliken, Bader, Hirshfeld, Weinhold, and VDD methods for charge analysis.

We present the Voronoi Deformation Density (VDD) method for computing atomic charges. The VDD method does not explicitly use the basis functions but calculates the amount of electronic density that flows to or from a certain atom due to bond formation by spatial integration of the deformation density over the atomic Voronoi cell. We compare our method to the well-known Mulliken, Hirshfeld, Bader, and Weinhold [Natural Population Analysis (NPA)] charges for a variety of biological, organic, and inorganic molecules. The Mulliken charges are (again) shown to be useless due to heavy basis set dependency, and the Bader charges (and often also the NPA charges) are not realistic, yielding too extreme values that suggest much ionic character even in the case of covalent bonds. The Hirshfeld and VDD charges, which prove to be numerically very similar, are to be recommended because they yield chemically meaningful charges. We stress the need to use spatial integration over an atomic domain to get rid of basis set dependency, and the need to integrate the deformation density in order to obtain a realistic picture of the charge rearrangement upon bonding. An asset of the VDD charges is the transparency of the approach owing to the simple geometric partitioning of space. The deformation density based charges prove to conform to chemical experience.

Journal Article↗