The Division of Bioinformatics (Medical Faculty; Head: Prof. Heinrich Sticht) applies molecular dynamics simulations to study the structure and interactions of proteins with a particular focus on their role in disease. The identification of the underlying principles of molecular recognition is important for the understanding of regulatory mechanisms and for the design of synthetic compounds that interfere with these processes. Research projects include host pathogen-interactions relevant for the emergence of diseases (funded within GRK2504) and the ligand binding properties of mutant G-protein-coupled receptors (funded within GRK1910).
Prof. Heinrich Sticht
PD Dr. Anselm Horn
Methods and Software
The most relevant software packages used in the group as well as some exemplary applications are given below:
– AMBER (GPU version): most protein systems (including membrane proteins)
– AMBER (CPU version): constant pH MD simulation
– AMBER: Gaussian-accelerated MD (developer version; Amber20)
– Gaussian/antechamber: Parametrization of posttranslational modifications and organic ligands
– Gromacs including plumed: metadynamics simulations
The group has developed force field parameters for posttranslationally modified amino acids and simulation protocols for computational titration experiments. Current work is on the further development of simulation protocols in the field of metadynamics and Gaussian-accelerated MD. The latter methods are used in order to capture slower dynamic processes in MD simulations, like larger-scale conformational transitions or ligand binding processes. For the application of Gaussian-accelerated MD, there is an ongoing tight collaboration and personnel exchange with the AMBER developer group of Prof. Yinglong Miao (University of Kansas, USA).
The major research interest within the Division of Bioinformatics is on the following topics:
– Analysis of host-pathogen interactions
– Aggregation behavior of the Aβ-peptide of Alzheimer’s disease
– Structure of receptor-ligand complexes
– pH-dependence of protein structure
– Structure-based evaluation of protein variants
Prof. Heinrich Sticht
- Söldner CA, Horn AHC, Sticht H. (2019) A Metadynamics-Based Protocol for the Determination of GPCR-Ligand Binding Modes. Int J Mol Sci. 20(8). pii: E1970.
- Diewald B, Socher E, Söldner CA, Sticht H. (2018) Conformational Dynamics of Herpesviral NEC Proteins in Different Oligomerization States. Int J Mol Sci. 19(10). pii: E2908.
- Socher E, Sticht H. (2016) Mimicking titration experiments with MD simulations: A protocol for the investigation of pH-dependent effects on proteins. Sci Rep. 3;6:22523.
- Homeyer N, Horn AHC, Lanig H, Sticht H. (2006) AMBER force-field parameters for phosphorylated amino acids in different protonation states: phosphoserine, phosphothreonine, phosphotyrosine, and phosphohistidine. J Mol Model. 12(3):281-9
Dr. Anselm Horn
- Huraskin D, Horn AHC. (2019) Alkali ion influence on structure and stability of fibrillar amyloid-β oligomers. J Mol Model. 25(2):37
- Socher E, Sticht H, Horn AHC (2014) The conformational stability of nonfibrillar amyloid-β peptide oligomers critically depends on the C-terminal peptide length. ACS Chem Neurosci. 5(3):161-7.
- Horn AHC (2014) A consistent force field parameter set for zwitterionic amino acid residues. J Mol Model. 20(11):2478.
- Kahler A, Sticht H, Horn AHC (2013) Conformational stability of fibrillar amyloid-beta oligomers via protofilament pair formation – a systematic computational study. PLoS One 8(7):e70521.