[gmx-users] about Normal Mode Analysis

[Anna Marabotti]

Dear All,
I'm trying to perform my first Normal Mode Analysis on a protein of 158 residues, therefore I read the Gromacs
manual searching for the proper way to do it.
I understand that the first step is a deep minimization of my protein, but when I tried to apply it to my
system, it failed to reach the required convergence. I tried several times without success. I'm using Gromacs
v. 3.3.3 which is compiled in double precision (I also checked in the .tpr file and it gives to me confidence
that the precision is really double, since coordinates are written with six decimals). I first made a steepest
descent EM, then I used the output .trr file as an input for grompp (the command was grompp_d -f emdeep.mdp -c
em1st.gro -t em1st.trr -o emdeep.tpr). My emdeep.mdp file was:

title               =  emdeep 
cpp                 =  /usr/bin/cpp
define              =  -DFLEXIBLE (however, I minimized the protein only, in vacuum)
constraints         =  none
integrator          =  cg
nsteps              =  20000
emtol               =  0.00001 
emstep              =  0.01, then 0.05, then 0.1
nstlist             =  5 
ns_type             =  grid
rlist               =  1.0
coulombtype         =  PME
rcoulomb            =  1.0
rvdw                =  1.0
fourierspacing	=  0.12
fourier_nx		=  0
fourier_ny		=  0
fourier_nz		=  0
pme_order		=  4
ewald_rtol		=  1e-5
optimize_fft		=  yes

The run did not reach convergence to the requested Emtol, the Fmax was oscillating around a value of 100.
Since the program claimed (as usually) that the stepsize was too short, I enlarged it, but nothing changed
with cg. I changed the integrator with l-bfgs, and it continued until 20,000 steps, without success (I noticed
that the Fmax was more or less the same during the whole minimization, so I don't think that it would be
useful to prolonge further the simulation). I also read the messages in the gmx-users list, but did not find
useful infos to solve my problem.
I would like to ask you two things. First of all, obviously, if you could help me to find what's wrong in my
settings and/or in my system. Then, my main doubt is how to set properly the .mdp file for minimization. Could
you inform me if there are somewhere tutorials related to NMA using GROMACS? I think that such kind of
exercise would be very useful: in fact, I think that it is not easy to translate the theory of NMA in practice
when you have to deal with all the parameters present in a .mdp file, and an example would serve as a starting
guideline.

Many thanks in advance for the help you would give me.
Best regards
Anna

______________________________________________
Anna Marabotti, Ph.D.
Laboratory of Bioinformatics and Computational Biology
Institute of Food Science, CNR
Via Roma 64
83100 Avellino (Italy)
Phone: +39 0825 299651
Fax: +39 0825 781585
Skype: annam1972
E-mail: amarabotti at isa.cnr.it
Web page: http://bioinformatica.isa.cnr.it/anna/anna.htm
____________________________________________________
"If you think you are too small to make a difference, try sleeping with a mosquito"