Re: [AMBER] relative binding free energy - tutorial a9

From: leila karami <>
Date: Mon, 5 Dec 2011 13:18:08 +0330

Dear Dr. Thomas Steinbrecher

Thanks for your reply

I use Amber10. Thus, it's would better to do simulation in multiple steps.

Is it true?

What points are important in free energy calculation for process such
as DNA mutation and should be considered?

In your tutorial, benzene changed to the phenol (transformation of the
H6 to O6_H6)
and in some studies, one residue of protein changed (for example; Ala to Gly).

I want to do mutate in DNA (for example; mutation GC base pair to AT base pair).

There are 2 questions:

1) In your and other cases, there is only one change. But in my case,
there is two changes
(G to A and C to T). How to manage this case?

2) If I only consider mutation of the G to A (both of G and A are
pyrimidine), difference of G and A is as follows:

G : C6=O6 A : C6-NH2
G : C6-N1-H1 A : C6=N1
G : C2-NH2 A : C2-H2

I wrote table being in tutorial as below:

prmtop: G step 1 prmtop: G
crgmask='' crgmask= C6, O6, N1, H1, N2, H21, H22
scmask='' scmask=''

prmtop: G step 2 prmtop: A
crgmask= C6, O6, N1, H1, N2, H21, H22 crgmask= C6, N6, H6, H62, N1, H2
scmask= C6, O6, N1, H1, N2, H21, H22 scmask= C6, N6, H6, H62, N1, H2
ifsc=1 ifsc=1

prmtop: A step 3 prmtop: A
crgmask= C6, N6, H6, H62, N1, H2 crgmask=''
scmask='' scmask=''

is it true?

Please guide me.
Best regards

On 12/4/11, <> wrote:
> Hi,
>> You broken up each transformation into three substeps : 1) Remove charges
>> from BNZ 2) Transform BNZ into PHN and 3) Add charges to PHN.
>> I want to know should I use 3 substeps also?
> You don't need to, since Amber11 can also do onestep transformations
> without first removing charges. Check Steinbrecher, Joung, Case, 2011, J
> Comp Chem (I think). However, it may be advantageous to do it in multiple
> steps. mutating DNA is a big change, so make sure that you have good
> experience using the TI code on smaller changes before you tackle such a
> big problem.
> Kind Regards,
> Thomas
> Dr. Thomas Steinbrecher
> formerly at the
> BioMaps Institute
> Rutgers University
> 610 Taylor Rd.
> Piscataway, NJ 08854
> _______________________________________________
> AMBER mailing list

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Received on Mon Dec 05 2011 - 02:00:03 PST
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