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Dirk Bakowies

Publications and source records attributed to Dirk Bakowies.

7 recordsLinked to original sources
PubMed2006

Biomolecular modeling: Goals, problems, perspectives.

Computation based on molecular models is playing an increasingly important role in biology, biological chemistry, and biophysics. Since only a very limited number of properties of biomolecular systems is actually accessible to measurement by experimental means, computer simulation can complement experiment by providing not only averages, but also distributions and time series of any definable quantity, for example, conformational distributions or interactions between parts of systems. Present day biomolecular modeling is limited in its application by four main problems: 1) the force-field problem, 2) the search (sampling) problem, 3) the ensemble (sampling) problem, and 4) the experimental problem. These four problems are discussed and illustrated by practical examples. Perspectives are also outlined for pushing forward the limitations of biomolecular modeling.

Computer Simulation↗
PubMed2005

The GROMOS software for biomolecular simulation: GROMOS05.

We present the latest version of the Groningen Molecular Simulation program package, GROMOS05. It has been developed for the dynamical modelling of (bio)molecules using the methods of molecular dynamics, stochastic dynamics, and energy minimization. An overview of GROMOS05 is given, highlighting features not present in the last major release, GROMOS96. The organization of the program package is outlined and the included analysis package GROMOS++ is described. Finally, some applications illustrating the various available functionalities are presented.

Algorithms↗
PubMed2005

Principles of carbopeptoid folding: a molecular dynamics simulation study.

The conformational spaces of five oligomers of tetrahydrofuran-based carbopeptoids in chloroform and dimethyl sulfoxide were investigated through nine molecular dynamics simulations. Prompted by nuclear magnetic resonance experiments that indicated various stable folds for some but not all of these carbopeptoids, their folding behaviour was investigated as a function of stereochemistry, chain length and solvent. The conformational distributions of these molecules were analysed in terms of occurrence of hydrogen bonds, backbone torsional-angle distributions, conformational clustering and solute configurational entropy. While a cis-linkage across the tetrahydrofuran ring favours right-handed helical structures, a trans-linkage results in a larger conformational variability. Intra-solute hydrogen bonding is reduced with increasing chain length and with increasing solvent polarity. Solute configurational entropies confirm the picture obtained: they are smaller for cis- than for trans-linked peptides, for chloroform than for dimethyl sulfoxide as solvent and for shorter peptide chains. The simulations provide an atomic picture of molecular conformational variability that is consistent with the available experimental data.

Computer Simulation↗
PubMed2003

Circular dichroism spectra of beta-peptides: sensitivity to molecular structure and effects of motional averaging.

Circular dichroism spectra of two beta-peptides, i.e. peptides composed of beta-amino acids, calculated using ensembles of configurations obtained by molecular dynamics simulation are presented. The calculations were based on 200 ns simulations of a beta-heptapeptide in methanol at 298 K and 340 K and a 50 ns simulation of a beta-hexapeptide in methanol at 340 K. In the simulations the peptides sampled both folded (helical) and unfolded structures. Trajectory structures with common backbone conformations were identified and grouped into clusters. The CD spectra were calculated for individual structures, based on peptide-group dipole transition moments obtained from semi-empirical molecular orbital theory and using the so-called matrix method. The single-structure spectra were then averaged over entire trajectories and over clusters of structures. Although certain features of the experimental CD spectra of the beta-peptides are reproduced by the trajectory-average spectra, there exist clear differences between the two sets of spectra in both wavelength and peak intensities. The analysis of individual contributions to the average spectra shows that, in general, the interpretation of a CD signal in terms of a single structure is not possible. Moreover, there is a large variation in the CD spectra calculated for a set of individual structures that belong to the same cluster, even when a structurally tight clustering criterion is used. This indicates that the CD spectra of these peptides are very sensitive to small local structural differences.

Circular Dichroism↗
PubMed2002

Water in protein cavities: A procedure to identify internal water and exchange pathways and application to fatty acid-binding protein.

A computational approach based on Delaunay triangulation is presented to identify internal water molecules in proteins and to capture pathways of exchange with the bulk. The implemented procedure is computationally efficient and can easily be applied to long molecular dynamics trajectories of protein simulations. In an application to fatty acid-binding protein in apo-form and with bound palmitate, several protein orifices known from crystal structures have been confirmed to be major portals of solvent exchange. Differences between the two forms of the protein are observed and discussed.

Algorithms↗
PubMed2002

Simulations of apo and holo-fatty acid binding protein: structure and dynamics of protein, ligand and internal water.

Two molecular dynamics simulations of 5 ns each have been carried out for rat intestinal fatty acid binding protein, in apo-form and with bound palmitate. The fatty acid and a number of water molecules are encapsulated in a large interior cavity of the barrel-shaped protein. The simulations are compared to experimental data and analyzed in terms of root mean square deviations, atomic B-factors, secondary structure elements, hydrogen bond patterns, and distance constraints derived from nuclear Overhauser experiments. Excellent agreement is found between simulated and experimental solution structures of holo-FABP, but a number of differences are observed for the apo-form. The ligand in holo-FABP shows considerable displacement after about 1.5 ns and displays significant configurational entropy. A novel computational approach has been employed to identify internal water and to capture exchange pathways. Orifices in the portal and gap regions of the protein, discussed in the experimental literature, have been confirmed as major openings for solvent exchange between the internal cavity and bulk water. A third opening on the opposite side of the barrel experiences significant exchange but it does not provide a pathway for further passage to the central cavity. Internal water is characterized in terms of density distributions, interaction energies, mobility, protein contact times, and water molecule coordination. A number of differences are observed between the apo and holo-forms and related to differences in the protein structure. Solvent inside apo-FABP, for example, shows characteristics of a water droplet, while solvent in holo-FABP benefits from interactions with the ligand headgroup and slightly stronger interactions with protein residues.

Animals↗