AMBER Archive (2007)

Subject: AMBER: Backbone stability problems with parm94, glycam04 and AMBER 8

From: Andrew Borgert (borg0109_at_umn.edu)
Date: Wed May 30 2007 - 12:35:51 CDT


I am attempting to run unrestrained MD on a small glycopeptide ( 9 amino
acid and 4 GalNAc) in explicit solvent using parm94, glycam04l (the
latest version) and AMBER8, however I am having problems with backbone
stability at the first glycosylated threonine. The most obvious symptom
of the instability is that the HA-CA-CO-O dihedral angle in the first
threonine switches from ~ -130 to ~ 60 degrees after several
nanoseconds, resulting in what could best be described as a 'kink' in
the glycopeptide.

Some important notes about the system and MD parameters:

This is definitely not a switch to the cis configuration

1 fs timestep.

The glycosylated threonine in question is preceded by two prolines, and
followed by 3 more glycosylated THR's and then the rest of the peptide.

The starting structure was initially produced with xplor using NOE and
coupling data and approximates a beta-strand across the THR's.

I am using a truncated octahedron box with a 'radius' of 9 angstroms
along with TIP3 water, PME and constant pressure.

The system temperature was run up to 300K over 20 ps with weak
restraints on the glycopeptide

I have attempted to stabilize the peptide by adding bulk (in this case 4
Ala's on each end) to the glycopeptide, but without success.

Run using 4 processors of a SGI/Linux machine

here is the sander input file for the unrestrained dynamics:

 &cntrl
  imin=0,
  irest = 1,
  ntx = 7,
  ntb = 2, pres0 = 1.0, ntp = 1, taup = 2.0,
  cut = 10,
  ntr = 0,
  ntc = 2,
  ntf = 2,
  tempi = 300.0,
  temp0 = 300.0,
  ntt = 3,
  gamma_ln = 1.0,
  nstlim = 1000000, dt = 0.001,
  ntpr = 200, ntwx = 200, ntwr = 200
 /

I would be grateful for any suggestions and/or for the pointing out of
any glaring errors.

Andrew Borgert
Biophysical Sciences and Medical Physics
University of Minnesota

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