Research Topics - Steered/Interactive Molecular Dynamics

Knowledge of the mechanism of association, dissociation and unfolding of macromolecules is important for many biological processes. Among the examples are the binding and dissociation of substrates of enzyme reactions, the recognition of ligands by their receptors or the elastic resopnse of mechanical proteins. In order to study such processes external forces can be applied reducing energy barriers and therefore increasing the probability of unlikely events on the time scale of molecular dynamics. This approach has the advantage that it corresponds closely to micromanipulation through atomic force microscopy or optical tweezers. The external force techniques can be applied to study many processes, including dissociation of avidin-biotin complex, dissociation of retinal from bacteriorhodopsin, stretching of titin, etc. The molecular dynamics program NAMD, developed in the group, is capable of performing several different kinds of SMD, including rotation or translation of one or more atoms. The group's molecular graphics program VMD provides a powerful means of visualizing these simulations, and through the Interactive Molecular Dynamics (IMD) interface can even allow SMD simulations to be performed in real time.

Single DNA strand permeates the pore of alpha-hemolysin

image size: 93.2KB
made with VMD
see a movie ( 3.9MB )

In a remote New Mexico dessert, Klaus Schulten met Amit Meller, who told him a story of two DNA hairpins. The first one, when threaded through the transmembrane pore of alpha-hemolysin blocks the ionic current to 12 pA and escapes from the pore about three times slower than the other one that blocks the current to only 9 pA. The amazing fact about these experiments was that the two DNA hairpins were identical in sequence. The only difference was in the global orientation of the single stranded part of the hairpin in the pore of alpha-hemolysin. Astonished by the outcome of their experiments, Amit Meller and Jérôme Mathé sought an explanation from the modelers (Klaus Schulten and Aleksei Aksimentiev). Cautious as the experimentalists are, they did not tell the modelers which of the DNA orientations produces the larger current blockade and which one escapes faster from the pore. We describe our quest for the solution of the puzzle.

All Spotlights


Onset of anthrax toxin pore formation. Mu Gao and Klaus Schulten. Biophysical Journal, 90:3267-3279, 2006.

What makes an aquaporin a glycerol channel: A comparative study of AqpZ and GlpF. Yi Wang, Klaus Schulten, and Emad Tajkhorshid. Structure, 13:1107-1118, 2005.

In search of the hair-cell gating spring: Elastic properties of ankyrin and cadherin repeats. Marcos Sotomayor, David P. Corey, and Klaus Schulten. Structure, 13:669-682, 2005.

Calculating potentials of mean force from steered molecular dynamics simulations. Sanghyun Park and Klaus Schulten. Journal of Chemical Physics, 120:5946-5961, 2004.

Insights into the molecular mechanism of rotation in the Fo sector of ATP synthase. Aleksij Aksimentiev, Ilya A. Balabin, Robert H. Fillingame, and Klaus Schulten. Biophysical Journal, 86:1332-1344, 2004.

Mechanisms of selectivity in channels and enzymes studied with interactive molecular dynamics. Paul Grayson, Emad Tajkhorshid, and Klaus Schulten. Biophysical Journal, 85:36-48, 2003.

Identifying unfolding intermediates of FN-III10 by steered molecular dynamics. Mu Gao, David Craig, Viola Vogel, and Klaus Schulten. Journal of Molecular Biology, 323:939-950, 2002.

Structural determinants of MscL gating studied by molecular dynamics simulations. Justin Gullingsrud, Dorina Kosztin, and Klaus Schulten. Biophysical Journal, 80:2074-2081, 2001.

Unfolding of titin immunoglobulin domains by steered molecular dynamics simulation. Hui Lu, Barry Isralewitz, André Krammer, Viola Vogel, and Klaus Schulten. Biophysical Journal, 75:662-671, 1998.

Molecular dynamics study of unbinding of the avidin-biotin complex. Sergei Izrailev, Sergey Stepaniants, Manel Balsera, Yoshi Oono, and Klaus Schulten. Biophysical Journal, 72:1568-1581, 1997.