 Research and Teaching Interests
Our research focuses on the conformational dynamics of proteins. Proteins are not static molecules; most proteins change shape during and part of their functional cycle. In fact, conformational changes are crucial for the proper functioning of many proteins. Although their biological role is generally understood, insights into the microscopic origins of these changes are still lacking. We aim to elucidate the fundamental principles responsible for the conformational behavior by a combination of existing and newly developed computational techniques.
• DNA binding proteins
We are particularly interested in sequence specific DNA binding proteins. Many DNA binding proteins fold upon binding their DNA target sequence, with some very interesting thermodynamic consequences. We use large-scale molecular dynamics simulations to investigate the mechanism of coupled protein folding and DNA binding.
• Bacteriological toxins
Certain bacteriological toxins undergo large conformational changes as part of their activation mechanism. We aim to uncover the interactions responsible for the motion by modeling techniques and computer simulations, which will aid our design of ligands to block the motion.
• Method development
The main hurdle for the study of conformational changes by computer simulations is the time scale of the transitions. We are working on new biasing methods that enforce the simulated transition in time scales accessible to molecular dynamics. In addition, we are developing new free energy methods for the calculation of minimum free energy pathways and free energy profiles for the conformational change.
Representative Publications
"Multiple scaling replica exchange for the conformational sampling of biomolecules in explicit water," H. Kamberaj and A. van der Vaart, J. Chem. Phys. 127, 234102 (2007).
"Minimum free energy pathways and free energy profiles for conformational transitions based on atomistic molecular dynamics simulations," A. van der Vaart and M. Karplus, J. Chem. Phys. 126, 164106 (2007).
"Simulation of conformational transitions," A. van der Vaart, Theor. Chem. Acc 116, 183 (2006).
"Simulation of conformational transitions by the restricted perturbation – targeted molecular dynamics method," A. van der Vaart and M. Karplus, J. Chem. Phys. 122, 114903 (2005).
"The unfolding action of GroEL on a protein substrate," A. van der Vaart,J. Ma, and M. Karplus, Biophys. J. 87, 562 (2004).
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