- Pär Söderhjelm (Senior lecturer)
- Soumendranath Bhakat (PhD student)
- Mandar Kulkarni (Post doc)
- .... Do you want to join our group? Contact us to discuss possible student projects, Master projects etc.
Former group members
- Ronja Lillienau (project student, 2018)
- Eric Fagerberg (Master student, 2016)
- Emil Åberg (Master student, 2016-2017)
- Johanna Schmidt (project student, 2015)
- Nils Hermansson Truedsson (project student, 2014)
- Teodor Rodin (project student, 2014)
Molecular dynamics of proteins
Molecular dynamics simulations offer a fantastic opportunity to see how proteins work. By following the movement of every single atom under the influence of the forces from all other atoms, we get an extremely detailed picture of protein dynamics. Thus, we can nowadays do discoveries in the supercomputer instead of in the lab.
However, there are two problems:
- The time interval that one can simulate (typically a microsecond) is too short for directly watching biologically interesting processes, such as conformational changes, ligand binding, and enzymatic reactions.
- The force fields used to model the interactions between atoms are not sufficiently accurate to always give reliable results.
We try to solve both these problems by developing new simulation algorithms and interaction models, as well as adapting existing methods to new systems. We validate the theoretical results by comparing to state-of-the-art dynamical NMR experiments. Our long-term goal is to understand proteins and the various functions they perform.
- Flap dynamics in aspartic proteases such as Plasmepsin and HIV protease
- Local unfolding of proteins: fundamental picture and comparison to hydrogen-deuterium exchange experiments
- Reconnaissance metadynamics: protein-ligand docking in the free-energy landscape
- Overcoming the sampling problem in FEP calculations of protein-ligand binding
- Accurate protein-ligand binding by funnel metadynamics
- Conformational changes in beta-adrenergic receptor upon agonist binding
- Solvation free energies using polarizable force fields
- PMISP: a method for computing protein-ligand interaction energies at a high QM level
- QM/MM methods with polarizable embedding
- P. Söderhjelm, G. A. Tribello, M. Parrinello; Locating binding poses in protein-ligand systems using reconnaissance metadynamics; Proc. Natl. Acad. Sci. USA, 109, 5170-5175 (2012)
- Y.-W. Hsiao, P. Söderhjelm; Prediction of SAMPL4 host–guest binding affinities using funnel metadynamics; J. Comput.-Aid. Mol. Design, 28, 443 (2014)
- M. Mahanti, S. Bhakat, U. J. Nilsson, P. Söderhjelm; Flap dynamics in Aspartic Proteases: A computational perspective, Chemical Biology & Drug Design, Chemical Biology & Drug Design, 8, 159 (2016)
- S. Bhakat, P. Söderhjelm; Resolving the problem of trapped water in binding cavities: prediction of host–guest binding free energies in the SAMPL5 challenge by funnel metadynamics, J. Comput. Aided Mol. Des. 31, 119 (2017)
- S. Bhakat, E. Åberg, P. Söderhjelm; Prediciton of binding poses to FXR using multi-targeted docking combined with molecular dynamics and enhanced sampling, J. Comput. Aided Mol. Des. 32, 59-73 (2018)
- P. Söderhjelm; Polarization effects in protein-ligand calculations extend farther than the actual induction energy, Theor. Chem. Acc. 131, 1159 (2012)
- F. Manzoni, P. Söderhjelm; Prediction of hydration free energies for the SAMPL4 data set with the AMOEBA polarizable force field; J. Comput.-Aid. Mol. Design, 28, 235 (2014)
- S. Genheden, U. Ryde, P. Söderhjelm; Binding affinities by free-energy perturbation using QM/MM with a large QM system and polarizable MM model; J. Comput. Chem. 36, 2114 (2015)
- M. Andrejic, U. Ryde, R. A. Mata, P. Söderhjelm; Coupled-cluster interaction energies for 200-atom host-guest systems, ChemPhysChem, 15, 3270 (2014)
- U. Ryde, P. Söderhjelm; Ligand-Binding Affinity Estimates Supported by Quantum-Mechanical Methods, Chemical Reviews, 116, 5520 (2016)
- F. Persson, P. Söderhjelm, B. Halle; The geometry of protein hydration, J. Chem. Phys. 148, 215101 (2018)
- F. Persson, P. Söderhjelm, B. Halle; How proteins modify water dynamics, J. Chem. Phys. 148, 215103 (2018)
- F. Persson, P. Söderhjelm, B. Halle; The spatial range of protein hydration, J. Chem. Phys. 148, 215104 (2018)