Re: [AMBER] QMMM of protein-ligand complex: Unable to achieve self consistency

From: M. L. Dodson <>
Date: Tue, 30 Mar 2010 10:09:27 -0500

On Mar 30, 2010, at 9:41 AM, Dmitri Nilov wrote:

> Hello! I try to use QMMM MD method realized in Amber10, and i've got a
> problem.
> QMMM minimization and simulation of my ligand in water box (ligand is QM
> part) run very well, but in minimization of ligand bound with protein (QM
> part is ligand or "ligand+key amino acid residue"), ligand exploded with
> warnings in output:
> QMMM: Unable to achieve self consistency to the tolerances specified
> QMMM: No convergence in SCF after 1000 steps.
> QMMM: Job will continue with unconverged SCF. Warning energies
> QMMM: and forces for this step will not be accurate.
> QMMM: E = -0.8502E+06 DeltaE = 0.1024E-07 DeltaP = 0.2569E-08
> QMMM: Smallest DeltaE = 0.1013E-07 DeltaP = 0.2645E-08 Step = 997
> 50 -2.4989E+05 1.3498E+01 1.8696E+02 CD2 12005
> BOND = 287.5026 ANGLE = 1680.2157 DIHED =
> 7289.6363
> VDWAALS = 9711.0237 EEL = -305100.5093 HBOND =
> 0.0000
> 1-4 VDW = 3111.1525 1-4 EEL = 32480.0419 RESTRAINT =
> 142.9937
> PM3ESCF = 511.4157
> EAMBER = -250029.5209
> Protein-ligand complex is based on crystallographic structure, thus, i
> believe that starting conformation is good.
> I've tried cut off 8, 9, 10; AM1 and PM3; SHAKE and NOSHAKE minimization.
> Example of input file is attached.
> Thanks a lot!

Do you equilibrate and run dynamics with a regular AMBER FF before you start QMMM? If not, I recommend you do so. (Use antechamber to parameterize your ligand. Since you will represent the ligand using QM for production runs, the antechamber am1bcc charges should be adequate for this preliminary step.) This relaxes the majority of the system to the AMBER FF. I run a regular AMBER equilibration regime, then 1ns of QMMM equilibration before I do whatever experiment I want to carry out (SMD in my case). I do not have the kind of problems you describe.

If you do not want to do that, at the very least, I would recommend you minimize the ligand by itself using sqm with the same semiempirical setup you will use for QMMM, then dock it back into the protein using RMS superposition methods, finally run your QMMM equilibration.

Good luck,
Bud Dodson
M. L. Dodson
Business email: activesitedynamics-at-comcast-dot-net
Personal email: mldodson-at-comcast-dot-net
Phone: eight_three_two-five_63-386_one
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Received on Tue Mar 30 2010 - 08:30:02 PDT
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