AMBER Archive (2003)

Subject: Re: MD input file for MM-PBSA calculations

From: Natasja Brooijmans (nbrooij_at_itsa.ucsf.edu)
Date: Sat May 24 2003 - 11:28:39 CDT

How much do the binding constants differ? Did you calculate the
translational, rotational, and vibrational entropy terms? It's very common
for MM-PBSA to overestimate stability, since induced fit is not taken into
account.

Natasja Brooijmans, Ph.D.
Visiting Post-Doctoral Scholar
Kuntz Laboratory
Department of Pharmaceutical Chemistry
University of California, San Francisco
San Francisco, CA 94143-2240
phone: 415-476 3986
fax: 415-502 1411
e-mail: nbrooij_at_itsa.ucsf.edu

On Sat, 24 May 2003, Thomas Steinbrecher wrote:

> Dear AMBER users,
>
> I am trying to perform MM-PBSA calculations on a protein
> ligand complex to estimate the ligands binding free energy.
> I had some troubles in reproducing measured binding
> constants and so I am checking what could have gone wrong.
>
> Could you comment on the input file below? I think it
> should generate trajectories that are suited to generate
> coordinate snapshots for MM-PBSA calculations. I plan to
> extract 100 snapshots after 10 ps each. My complex was
> equilibrated for 25ps before.
> I am a beginner in the field of molecular dynamics, so I am
> not sure if I overlooked some significant parameter or set
> all variables to reasonable values.
>
> Thank you in advance for any comments.
>
> Kind regards,
>
> Thomas Steinbrecher
>
> My AMBER7 input file for sander:
> ----------
> cons pressure second production with T300K
> &cntrl
> imin = 0, nmropt = 0, ntx = 1, irest = 0,
> ntrx = 1, ntxo = 1, ntpr = 5000, ntave = 0,
> ntwr = 5000, iwrap = 0,
>
> ntwx = 5000, ntwv = 0, ntwe = 0, ioutfm = 0,
> ntwprt = 0, idecomp = 0,
>
> ntf = 2, ntb = 2, dielc = 1, cut = 12.0,
> scnb = 2.0, scee = 1.2, nsnb = 10, ipol = 0,
>
> ibelly = 0, ntr = 0,
>
> nstlim = 500000, nscm = 0, t = 0.0, dt = 0.002,
>
> temp0 = 300.0, tempi = 300, ig = 71277,
> heat = 0.0, ntt = 1, vrand = 0, tautp = 1,
> vlimit = 20.0,
>
> ntc = 2, tol = 0.00001,
>
> ntp = 1, pres0 = 1.0, comp = 44.6, taup = 1,
> &end
> ----------
>
>