AMBER Archive (2008)

Subject: Re: AMBER: Input file for Minimization

From: Carlos Simmerling (carlos.simmerling_at_gmail.com)
Date: Tue Feb 12 2008 - 11:55:18 CST

Patrick,
I think your expectations from MD are not very realistic.
300AA is many orders of magnitude more difficult than
the 20AA that we successfully did in that publication.
MD is not a feasible way to predict structure for such a large
protein. I strongly suggest reading some of the literature on
the protein structure prediction field, particularly the results of
the CASP competitions. Your only real hope is to have a
known structure for a homologous sequence- and even then
there are lots of things that can go wrong and it's not very practical
unless you have a lot of experience with structural biology.
I think it would be best to work with someone that has that
kind of experience already- perhaps read some papers and
contact the ones that seem to do best on the kind of system
that you have, and see if they are interested in collaboration.
good luck!
CS

On Feb 12, 2008 12:43 PM, Campbell, Patrick <pcampbell_at_msm.edu> wrote:
>
>
>
> Hello Dr. Walker,
>
>
>
>
> Thanks for your prompt and precise response to my questions!
> I apologise for not being too explicit in my initial explanation - allow me
> to try again.
>
> I would like to examine the 'most stable' conformation of the 300aa protein
> based solely on its aa sequence - currently, it has no PDB file.
>
> Towards this end, I would employ minimization before MD to ultimately obtain
> the stable folding pattern of the protein in two states - in vacuo and
> solvated in water. My understanding is that I will have to do the
> minimization (to clean up the structure) before the MD - (the MD employs
> both heating and equilibration of the structure as per files heat1.in and
> equil.in shown below). At the end of the day, I would like to simulate
> binding interactions that exist between this protein and some selected
> ligands.
>
> My question is this:
> Following on your suggestion on explicit solvent environment, simulated
> annealing and cooling down to zero K, could you point me as to where I can
> obtain information (or the script itself) or the parameters for this
> simulation as it relates to the minimization, heating and equilibration
> steps? I am fairly new to AMBER and have not fully exhausted all of the
> reading material on the topic.
>
> Thank you so much for all your help Dr. Walker and do have a great day!
> Patrick
>
>
>
> equil.in
> Stage 2 equilibration 1 0-5ns
> &cntrl
> imin=0, irest=1, ntx=5,
> nstlim=2500000, dt=0.002,
> ntc=2, ntf=2,
> ntt=1, tautp=0.5,
> tempi=325.0, temp0=325.0,
> ntpr=500, ntwx=500,
> ntb=0, igb=1,
> cut=999.,rgbmax=999.
> /
>
> heat.in
>
> Stage 1 heating of TC5b 0 to 50K
> &cntrl
> imin=0, irest=0, ntx=1,
> nstlim=10000, dt=0.0005,
> ntc=2, ntf=2,
> ntt=1, tautp=1.0,
> tempi=0.0, temp0=50.0,
> ntpr=50, ntwx=50,
> ntb=0, igb=1,
> cut=999.,rgbmax=999.
> /
>
>
> ________________________________
>
> From: owner-amber_at_scripps.edu on behalf of Ross Walker
> Sent: Sun 2/10/2008 12:55 PM
> To: amber_at_scripps.edu
> Subject: RE: AMBER: Input file for Minimization
>
>
>
>
> Hi Patrick,
>
> This really depends on what you mean by the term minimize and what you want
> to do with the resulting structure. Note the file below will certainly
> minimized your structure (in implicit solvent) however it will only take you
> to the nearest local minimum which will mean you won't get much change in
> structure. If you want to explore more of the local phase space then you can
> try simple simulated annealing and then cooling down to zero K. Beyond that
> you will have to start looking in to procedures like replica exchange or
> other more complex approaches.
>
> The minimization from the tutorial you are referring to was purely to "clean
> up" the structure prior to running molecular dynamics on the system.
>
> Also note that a 200aa protein in explicit solvent is going to be very slow,
> you are probably better doing things in explicit solvent.
>
> All the best
> Ross
>
> /\
> \/
> |\oss Walker
>
> | Assistant Research Professor |
> | San Diego Supercomputer Center |
> | Tel: +1 858 822 0854 | EMail:- ross_at_rosswalker.co.uk |
> | http://www.rosswalker.co.uk | PGP Key available on request |
>
> Note: Electronic Mail is not secure, has no guarantee of delivery, may not
> be read every day, and should not be used for urgent or sensitive issues.
>
>
>
> ________________________________
> From: owner-amber_at_scripps.edu [mailto:owner-amber_at_scripps.edu] On Behalf Of
> Campbell, Patrick
> Sent: Saturday, February 09, 2008 13:19
> To: amber_at_scripps.edu
> Subject: AMBER: Input file for Minimization
>
>
>
> Hello All,
>
> I would like some information concerning the parameters to set for a
> minimization of a 200 aa, 30 kD protein. I was following from the AMBER
> tutorial by Ross Walker, and was wondering if the min1.in file which he
> quotes from the Simmerling, Strockbine and Roitberg paper could be modified
> for this process.
>
> min1.in
>
> Stage1 - minimisation of TC5b
> & cntrl
> imin=1, maxcyc=1000, ncyc=500,
> cut=999., rgbmax=999., igb=1, ntb=0,
> ntpr=100
> /
>
> If this file could be modified, could you suggest some parameters for this
> process.
>
> Thanks again for all your help.
>
> Pat
>
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