AMBER Archive (2004)

Subject: Re: AMBER: ptraj analyze matrix entropy

From: Holger Gohlke (gohlke_at_bioinformatik.uni-frankfurt.de)
Date: Wed May 05 2004 - 11:32:23 CDT

Marcin Krol schrieb:
>
> Dear Holger
> Thank you for your answer
>
> I still have a couple of questions:
> 1. I am using MM-PBSA to calculate free energy of binding and I want to
> include entrophy in my calculations. The initial values in the examples
> script perform the minimization of the structure, before nmode is run, to
> DRMS=0.1. I found your e-mail at the amber forum that this is way too much
> and should be changed to DRMS=0.0001 (at least). Then, I have to increase
> MAXCYC as well. The problem is, I am not sure that I get 0.0001 gradient
> at all using Conjugate-Gradient minimization method. I think, it would be
> better to run mode twice after the minimization in sander: first to futher
> minimize the structure in nmode using Newton-Raphson algorithm and then to
> calculate normal modes. Is there an easy way to force mm_pbsa.pl to run
> nmode twice (first for minimizaltion, then for normal modes)? Or maybe
> this is not necessary and conjugate gradient will do its job (I am just
> testing it and increades MAXCYC to 10000 and it looks like it is
> oscillating)

Since the NR minimization (in general) involves the calculation and
diagonalization of the Hessian matrix in every step, it is very costly
to apply to larger systems. From my experience, CG minimization led to a
rms value of the gradient < 0.0001 for a 250 residue protein in about
12000 steps. You mention oscillating rms values of the gradient - do you
use a nonbonded cutoff that is larger than your system size?

Best regards

Holger

>
> Best wishes
> marcin
>
> > > I wonder how the entropy is calculated by ptraj analyze matrix thermo
> > > command. Is this obtained from a quasiharmonic analysis?
> >
> > Yes, the "ptraj analyze matrix thermo" command should give identical
> > results to the quasih program.
> >
> > > What is the
> > > diffrence between entropy calculated in nmode (mm_pbsa.pl script) and
> > > analyze matrix?
> >
> > nmode does a normal mode analysis (i.e. you diagonalize a Hessian matrix
> > obtained from a single conformation residing at a minimum of the
> > potential energy surface), thus you approximate your potential energy
> > surface at that point by a harmonic model.
> >
> > analyze matrix calculates a (mass-weighted) covariance matrix from a
> > trajectory, whereby the inverse of this matrix is related to a "quasi"
> > Hessian matrix. In this "quasiharmonic" analysis, some effects of
> > anharmonic terms in the potentials are included, as are e.g. solvent
> > effects. When calculating entropies by this approach, you need to check
> > the convergence of your results, though.
> >
> > > Could you point me to an article describing how the
> > > entropy in the analyze matrix command is obtained.
> >
> > A good starting point is Curr Opin Struct Biol 1994, 4, 285-290. In
> > particular see ref. 26 and 27 therein.
> >
> > Best regards
> >
> > Holger
> >
> > >
> > > Thank you in advance
> > > marcin
> > >
> > > Dr Marcin Krol
> > > Zaklad Bioinformatyki Collegium Medicum UJ
> > > Kopernika 7E
> > > 31-501 Krakow
> > > tel/fax (012) 422-77-64
> > > e-mail mykrol_at_cyf-kr.edu.pl
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> > --
> > ++++++++++++++++++++++++++++++++++++++++++++++++++
> > Dr. Holger Gohlke
> >
> > J.W. Goethe-Universität
> > Fachbereich Biologie und Informatik
> > Institut für Mikrobiologie
> > Marie-Curie-Str. 9
> > 60439 Frankfurt/Main
> > Germany
> >
> > Tel.: (+49) 69-798-29411; Fax: (+49) 69-798-29826
> > Email: gohlke_at_bioinformatik.uni-frankfurt.de
> > URL: http://www.rz.uni-frankfurt.de/~hgohlke
> > ++++++++++++++++++++++++++++++++++++++++++++++++++
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-- 
++++++++++++++++++++++++++++++++++++++++++++++++++                             
Dr. Holger Gohlke

J.W. Goethe-Universität
Fachbereich Biologie und Informatik
Institut für Mikrobiologie	
Marie-Curie-Str. 9              
60439 Frankfurt/Main            
Germany                         

Tel.:  (+49) 69-798-29411; Fax: (+49) 69-798-29826
Email: gohlke_at_bioinformatik.uni-frankfurt.de
URL:   http://www.rz.uni-frankfurt.de/~hgohlke
++++++++++++++++++++++++++++++++++++++++++++++++++
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