Jan Henning Peters

• Phd
• Researcher at Freie Universität Berlin

We describe simulations of Proteins and artificial pseudo-molecules interacting and shaping lipid bilayer membranes. We extract protein diffusion Parameters, membrane deformation profiles and the elastic properties of the used membrane models in preparation of calculations based on a large scale continuum model.

We extend the application of the adaptive resolution technique (AdResS) to liquid systems composed of alkane chains of different lengths. The aim of the study is to develop and test the modifications of AdResS required in order to handle the change of representation of large molecules. The robustness of the approach is shown by calculating several...

Molecular dynamics simulations enable access to free energy differences governing the driving force underlying all biological processes. In the current chapter we describe alchemical methods allowing the calculation of relative free energy differences. We concentrate on the binding free energies that can be obtained using non-equilibrium approaches...

In a conformational selection scenario, manipulating the populations of binding-competent states should be expected to affect protein binding. We demonstrate how in silico designed point mutations within the core of ubiquitin, remote from the binding interface, change the binding specificity by shifting the conformational equilibrium of the ground-...

It is emerging that not only protein structure, but also protein dynamics and conformational equilibria in proteins control to an important extent protein function. This holds for enzymes, where often conformational transitions determine the overall rate, but also for protein-ligand or protein-protein recognition. When nature makes use of the confo...

Motion is involved in a large number of protein functions. For ubiquitin, residual dipolar coupling (RDC) derived ensembles have suggested it recognizes binding partners via conformational selection through motions occurring on the supra tau-c (>4 ns) timescale [1]. Subsequent relaxation dispersion (RD) studies identified microsecond fluctuations f...

Simulation ensembles cover the same conformational space as known experimental structures. PCA projection of unbound MD simulation (starting structure 1ubi, red and a collection of experimental xray (black, 139 structures from 63 different PDB entries) and NMR (blue, 783 structures from 35 different PDB entries) structures. (TIFF)

Projection to higher order eigenvectors shows no significant differences between bound and unbound ensembles. Projection to PCA-eigenvectors 5 and 6 of all simulated bound ensembles based on the backbone of ubiquitin residues 1–70. For comparison, the unbound reference ensemble is also plotted in blue, the original xray structures are marked in yel...

Comparison of PCA eigenvectors based on all trajectories and unbound trajectories only. Inner product calculated between the first 10 eigenvectors of both PCAs. (TIFF)

Cross correlation test of PLS-DA models. Correlation between target and model for training (green) and test (orange) set for PLS-DA between unbound and bound ensembles based on backbone atoms of residues 1–70 evaluated for different basis dimensionality. (TIFF)

The importance of the hydrophobic patch in ubiquitin binding. Distance of the ubiquitin residues in all complexes from the binding partner. Residues Leu-8, Ile-44 and Val-70 (the “hydrophobic patch) have been marked in red. With two exceptions (Ile-44 and Val70 in complex 2g45) all hydrophobic patch residues are within of the binding partner. (TIFF...

Bound ensembles show significant structural dynamics. Conformational entropy observed in unbound (blue) and bound (red) simulation ensembles estimated according to the Schlitter formula excluding (A) and including (B) the flexible C-terminus. (TIFF)

Eigenvalue spectrum for the first 50 eigenvectors of the PCA used in the main paper (backbone atoms 1–70). (TIFF)

Projection to higher order eigenvectors shows no significant differences between bound and unbound ensembles. Projection to PCA-eigenvectors 7 and 8 of all simulated bound ensembles based on the backbone of ubiquitin residues 1–70. For comparison, the unbound reference ensemble is also plotted in blue, the original xray structures are marked in yel...

Coverage of different ensembles by the unbound reference ensemble. The histogram-coverage of bound ensembles (red) compared to coverage of unbound control ensembles (blue) after projection of the structures onto the first PCA-eigenvector (fig. 2) of backbone atoms of residues 1–76 (A), the PLS-DA difference vector of backbone atoms of residues 1–76...

Influence of sampling on ensemble coverage. Comparison of the results illustrated in 5 B (here: A) and C (here: B) for two different sampling frequencies, (green) and (orange). (TIFF)

Projection to higher order eigenvectors shows no significant differences between bound and unbound ensembles. Projection to PCA-eigenvectors 3 and 4 of all simulated bound ensembles based on the backbone of ubiquitin residues 1–70. For comparison, the unbound reference ensemble is also plotted in blue, the original xray structures are marked in yel...

Alternative PCA including all backbone atoms of ubiquitin. Projection to the first two PCA-eigenvectors of all simulated bound ensembles based on the backbone of all ubiquitin residues (1–76). For comparison, the unbound reference ensemble is also plotted in blue, the original xray structures are marked in yellow. Histograms for the projection on t...

Comparison of PCA eigenvectors based on all trajectories and bound trajectories only. Inner product calculated between the first 10 eigenvectors of both PCAs. (TIFF)

Protein-protein interactions play an important role in all biological processes. However, the principles underlying these interactions are only beginning to be understood. Ubiquitin is a small signalling protein that is covalently attached to different proteins to mark them for degradation, regulate transport and other functions. As such, it intera...

Protein-protein interactions play an important role in all biological processes. However, the principles underlying these interactions are only beginning to be understood. Ubiquitin is a small signalling protein that is covalently attached to different proteins to mark them for degradation, regulate transport and other functions. As such, it intera...

The Design of Experiments (DoE) approach is used to build models of beamlet parame- ters as the extracted beamlet current, beamlet divergence and the perveance limit in de- pendence on grid parameters and plasma density employing our well-approved beamlet simulation code. Appropriate polynomial degrees for the input parameters are determined which...