Institute_

Group_

Institut für Medizinische Optik, Theoretische Biophysik
Ludwig-Maximilians-Universität München
Theresienstraße 37, D-80333 München, Germany
e-mail: Helmut.Grubmueller@imo.physik.uni-muenchen.de

Predicting slow structural transitions in macromolecular systems: conformational flooding

Helmut Grubmüller

Sat Nov 4 00:01:20 MET 1995

Abstract:

We present a method to predict complex structural (conformational) transitions in irregular or disordered macromolecular systems such as proteins or glasses at the atomic level. Our method aims at rare events, which currently cannot be predicted with traditional molecular dynamics (MD) simulations, since these currently are limited to time scales shorter than a few nanoseconds. Given an initial conformation of the system, our method identifies one or more product states, which may be separated from the initial state by free energy barriers that are large on the scale of thermal energy. It also provides an approximate reaction path, which can be used to determine barrier heights or reaction rates with the usual techniques. The method employs an artificial potential that destabilizes the initial conformation and, thereby, lowers free energy barriers of structural transitions. As a result, transitions are accelerated and may be observed in MD-simulations. An analytical estimate for the acceleration factor is given. The method is applied to two test systems, an argon microcluster and a simplified protein model. By these studies we demonstrated that our method is capable to shorten mean transition times from s (argon cluster) and ns (protein model) to a few picoseconds. These results suggest that our method is particularly well suited to study biochemically relevant conformational motions in proteins at a microsecond time scale.

PACS numbers: 87.15.He, 82.20.Fd, 87.15.By, 82.20.Wt

• Introduction
• Theory
  • The subcanonical ensemble
  • Free energy in conformation space
  • Conformational coordinates, effective Hamiltonian
  • Conformational flooding
  • Estimate of transition rates
  • Adiabatic correction to Eq. (2.26)
  • Relaxation correction to Eq. (2.26)
• Two sample applications
  • Structural transitions in an argon cluster
    • Methods
    • Results and Discussion
  • Conformational transitions in a simplified protein model
    • Methods
    • Results and Discussion
• Summary and Conclusion
• References
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