AMBER Archive (2008)

Subject: Re: AMBER: umbrella sampling for proton transfer

From: Thomas Steinbrecher (steinbrt_at_scripps.edu)
Date: Tue Mar 25 2008 - 20:11:58 CDT

Hi Amara,

you are using SHAKE in your simulation which constrains the length of
bonds involving hydrogen atoms. I assume thats what you are seeing in your
output, an S-H distance being kept at its initial value. See the manual
sections on ntc and ntf for controls of the SHAKE algorithm.

>From the input file you provided, you are running only 5000 steps of MD
which seems to me a very small amount even for the simplest of umbrella
sampling simulations, let alone one involving a protein.

And last, the probably most serious point is that your simulation seems to
involve no QM potential. You cannot simulate reaction mechanisms with
classical MD as the proton will never leave the sulfur it is bonded too.

Kind Regards,

Dr. Thomas Steinbrecher
The Scripps Research Institute
10550 N. Torrey Pines Rd.
San Diego CA 92037, USA
> Hi, all,
>
> As a new user for amber, I am trying to run some umbrella sampling to study
> the catalytic reaction of an enzyme using AMBER9. The reaction involves a
> proton being transferred from S-H of a cys to N of a His. Following is the
> input file:
>
> &cntrl
> imin = 0,
> ntx = 7, irest = 1,
> ntb = 2, pres0 =1.0, ntp = 1,
> taup = 2,
> ntr = 0,
> cut = 20,
> ntc = 2, ntf = 2,
> tempi = 300.0, temp0 = 300.0,
> ntt = 3,
> gamma_ln = 1.0,
> nstlim = 5000, dt = 0.001,
> ntpr = 1, ntwx = 500, ntwr = 1000,
> nmropt = 1
> /
> &wt type = 'DUMPFREQ', istep1 = 10 /
> &wt type = 'END' /
> DISANG = s_h_n.RST
> DUMPAVE = s_h_n_vs_t.1
>
> and s_h_n.RST is
> &rst iat = 2238,2239, r1=0.0, r2=1.5, r3=1.5, r4=90.0, rk2=50., rk3=50., /
> &rst iat = 615,2239, r1=0.0, r2=2.5, r3=2.5 r4=99.0, rk2=50., rk3=50., /
>
> and part of result of s_h_n_vs_t.1 is
> 0 1.336 2.705
> 10 1.336 2.486
> 20 1.336 2.407
> 30 1.336 2.567
> 40 1.336 2.481
> 50 1.336 2.413
> 60 1.336 2.494
>
> The hydrogen atom in question is initially bonded to S @ 1.3 ang, I would
> like to simulate this proton leaving the sulfur atom and moving closer to a
> nearby nitrogen (initially at 2.7 ang).
>
> My questions are:
> 1. why the distance between S and H stays at the same value? I tried to
> increase the value of rk2 and rk3 to something like 500, but S-H still keeps
> at 1.336. I made a test run to increase the distance between convalently
> bonded S and C, and the value of S-C distance did change. So I guess there
> must be something special to deal with hydrogen in Amber. Am I right? What
> should I do to deal with this problem?
> 2. Am I right to use more than one restraints in s_h_n.RST to run umbrella
> sampling (like reaction coordinate R=r1-r2)? In fact, my "real" mechanism
> will likely involve more than 3 restraints.
>
> Thanks in advance to anyone that will give any suggestion.
>
>
> Amara
>
>
>
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