Crown Ether Demo

In this demo, we build a simple crown ether, put a Na+ ion in it, equilibrate the system (and use this to explore vacuum dynamics), and perturb the ion (first Na+ -> K+, then K+ -> Cs+), analyzing the trajectories. We also build a solvated model using polarizable atoms, and energy minimize it.

The non-bonded parameters used for the ions are not the standard force field file ones derived from Aqvist, as these were parameterized for interactions with water (for more on this distinction, see Ross & Hardin reference, below).

Since the atomic charges were derived in the distant past, the 1-4 charge-scaling factor SCEE is set to 2.0 in all simulations, even though the crown vdw and bonding parameters are from the newer Cornell et al. force field.

Examples

• setup/ Setup using Leap:
  • Build residue template 'CR'
  • Load pdb of whole molecule
  • Add complexed ion
  • Add perturbation to ion
  • Save 'parm' files for normal modes, dynamics & perturbation
• nmode/ Normal mode analysis of crown using Nmode:
  • Energy minimize
  • Frequencies and thermodynamic analysis
• dynamics/ Equilibration using Sander:
  • Run dynamics to equilibrate
  • Run constant-energy dynamics to understand energy loss
  • Run various constant-temperature schemes to explore equipartition
• pert/ Perturbation using Gibbs:
  • Run perturbation forward/back
  • Run some plain dynamics in the perturbed state
  • Optionally vary parameters
• analysis/ Trajectory analysis using Carnal:
  • Analyze trajectories

Related material, not necessary to understanding the demo:

 Dang LX.
     Mechanism and thermodynamics of ion selectivity 
	in aqueous solutions of 18-crown-6 ether -
	a molecular dynamics study.
     Journal of the American Chemical Society, 1995 Jul 5 V117 N26:6954-6960.

 Sun Y, Caldwell JW, and Kollman PA.
     Molecular Dynamics and Free Energy Perturbation Study of
	Spherand Complexation with Metal Ions Employing Additive
	and Nonadditive Force Fields.
     Journal of Physical Chemistry, 1995 V99, 10081-10085.

 Bayly CL and Kollman PA.
     Molecular Dynamics and Free Energy Calculations on the Peculiar
	Bimodal Alkali Ion Selectivity of an 8-Subunit Cavitand.
     Journal of the American Chemical Society, 1994 V116 N2:697-703.

 Billeter M, Howard AE, Kuntz ID, Kollman PA.
     A new technique to calculate low-energy conformations of
	cyclic molecules utilizing the ellipsoid algorithm
	and molecular dynamics: application to 18-crown-6.
     Journal of the American Chemical Society, 1988, Dec 7 V110 N25:8385-8391.


 Ross WS and Hardin CC.
     Ion-Induced Stabilization of the G-DNA Quadruplex: 
        Free Energy Perturbation Studies.
     Journal of the American Chemical Society, 1994, V116, N14:6070-6080.