questions regarding ABF sampling in a DMPC bilayer

From: Ajasja Ljubetič (ajasja.ljubetic_at_gmail.com)
Date: Wed Jan 18 2012 - 08:12:20 CST

Dear all,

For the past half-year I had a lot of fun building a GPU cluster and
running some ABF MD simulations in a DMPC bilayer. The system simulated is
a spin-labelled peptide composed of alanine either in water or in a DMPC
membrane (Fig1<http://lbf.ijs.si/ajasja/mails/ABF/enhancing-abf-DMPC/Fig1.GIF>
). The colvars (theta and phi) are the polar angles from the C-beta to the
center of mass of the ring of the spin label.
(Fig1<http://lbf.ijs.si/ajasja/mails/ABF/enhancing-abf-DMPC/Fig1.GIF>
).

And in that time I have gathered quite a few ABF related questions:

   - *Why is the diffusion along the colvars so much slower in a DMPC
   bilayer than in water? *For example compare the colvar trajectories of
   Fig2 <http://lbf.ijs.si/ajasja/mails/ABF/enhancing-abf-DMPC/Fig2.GIF>
(water)
   and Fig3 <http://lbf.ijs.si/ajasja/mails/ABF/enhancing-abf-DMPC/Fig3.GIF>(DMPC).
If the PMF along the colvars is approx flat, should it still matter
   that one system is in DMPC and another in water? So, is the slower
   diffusion an intrinsic property of the system or am I perhaps not setting
   some ABF parameters correctly?
   - *Why are there spikes in the forces applied by ABF in DMPC?* If one
   plots the applied forces in water and DMPC the patterns seems quite
   different. Larger forces are probably required to move lipid tails so
   perhaps this is normal.
Fig3<http://lbf.ijs.si/ajasja/mails/ABF/enhancing-abf-DMPC/Fig3.GIF>
(fa_theta
   and fa_phi)
   - *Why are there such small energy differences in PMF between water an
   DMPC? *(Fig4<http://lbf.ijs.si/ajasja/mails/ABF/enhancing-abf-DMPC/Fig4.GIF>).
   If the diffusion along the colvars is slower and more energy is needed to
   move lipids out of the way, then this should be seen in the PMF as higher
   energy barriers, right? But i'm seeing differences of only 2 kt, which does
   not seem that much. I thought this might be due to the fact that I'm
   running the simulations above the DMPC transition temperature. So I tried
   to lower the temperature (perhaps a bit too much), but at the lower
   temperature ABF fails to sample the phase-space very well
(Fig5<http://lbf.ijs.si/ajasja/mails/ABF/enhancing-abf-DMPC/Fig5.GIF>
   ).

   - *How are gradients merged using InputPrefix?* From some quick plots (
   Fig6 <http://lbf.ijs.si/ajasja/mails/ABF/enhancing-abf-DMPC/Fig6.GIF>)
   the algorithm seems to adjust the offset (how?) and make the
   gradient continuous. Overlapping regions are probably averaged over and the
   counts of the overlap summed.
   - *Is it possible to use Accelerated MD with ABF (and get correct
   results)?* This is more of a brainstorming question. Using aMD I could
   "soften up" the lipid tails, but this seems very similar to increasing
   the temperature, which means I would not know at what temperature and what
   phase (liquid ordered, liquid disordered) the lipids are. If indeed this is
   even technically possible.

Any insight is appreciated.

Thank you and best regards,
Ajasja Ljubetic,
lbf.ijs.si

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