Dynamic Protonation of Titratable Groups in Biomolecules for Molecular Dynamics Simulations
نویسنده
چکیده
Properties of biomolecules are often investigated using Molecular Dynamics (MD) simulations whereby atoms and molecules interact for a period of time, thus revealing the time dependent behavior of the system. Whereas the atom positions of the starting structures for such MD runs are usually derived from X-ray crystallography or NMR experiments, properties such as charges or bonds are specified in so called topologies fitted to the starting structure. During classical MD simulations such a predefined topology is not altered during the complete simulation run. Inherently this requires the protonation states of all titratable groups in bio molecules, e.g. glutamic acid, histidine, lysin etc., to remain unchanged during the full simulation. In this thesis we apply and extend a novel method, so called λ-dynamics, to allow topology switching between different protonation states as a dynamical process. Hereby two Hamiltonians are defined in advance reflecting the protonated and unprotonated configuration. The newly introduced parameter λ is a switching parameter on a linear interpolation of those Hamiltonians treated as a virtual dynamical particle. The forces acting on λ are derived from the derivative of the free energy landscape δG δλ . Hydration free energies for deprotonation are included by empirically altering the energy landscape in G. By accounting for the pH dependence of the hydration free energy in the energy landscape correction, constant pH simulations can be achieved. In an extended version of this method multiple titratable groups can be treated independently to allow molecular dynamics simulations of typical peptides and proteins.
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