hi all,
I have some followup questions. So I'm calculating the relative binding
free energy of changing REF.A1 to NEW.B1. I did it in three ways, one of
which uses soft-score potential while the other two don't. So for the two
that do NOT use soft-core potential, these are my input:
ifce=1, ifsc=0, crgmask='',scmask=':REF.A1',
ifce=1, ifsc=0, crgmask='',scmask=':NEW.B1',
or
ifce=1, ifsc=0, crgmask='',scmask=':REF',
ifce=1, ifsc=0, crgmask='',scmask=':NEW',
As Dr. Steinbrecher pointed out, in the second calculation, the two TI
calculations don't "see" each other. However in the first they should as I
understand. But they gave out almost the same result. This is the output
from calculation 1.
water complex dv/dl rms dv/dl rms 0.05 105.74 15.16 103.96 14.80 0.10
91.36 14.97 90.25 14.66 0.20 64.18 14.80 64.00 14.51 0.30 37.39 14.66
37.40 14.52 0.40 10.31 14.93 10.55 14.61 0.50 -17.05 15.01 -15.76 14.79
0.60 -44.81 15.43 -43.28 15.21 0.70 -73.09 15.23 -70.83 15.29 0.80 -101.90
15.33 -101.23 15.36 0.90 -131.21 15.96 -130.08 15.60 0.95 -146.08 15.55
-145.56 15.71 -18.52 15.16 -18.07 14.99
So it doesn't seem right to me that I'm getting the same DV/DL values when
you are just changing atom A1 to atom B1 and when you are changing the
whole molecule REF to molecule NEW. Also the rms values are big.
So I also turned on the soft-core potential (though not absolutely
necessary coz i have no additional atoms appearing or disappearing). This
is my input:
ifce=1, ifsc=1, crgmask='',scmask=':REF.A1',
ifce=1, ifsc=1, crgmask='',scmask=':NEW.B1',
And this is what I got:
water complex dv/dl rms dv/dl rms 0.05 0.81 1.85 -0.94 1.43 0.10 1.21
1.80 -0.43 1.46 0.20 2.16 2.03 0.63 1.88 0.30 2.94 2.85 1.60 2.39 0.40
2.95 3.66 2.33 2.82 0.50 2.30 3.50 3.18 3.38 0.60 1.62 3.05 3.44 4.03
0.70 1.12 2.72 2.90 4.38 0.80 0.70 2.44 2.75 4.35 0.90 0.38 2.27 2.12 4.36
0.95 0.22 2.27 1.87 4.19 1.56 2.64 1.86 3.18
The final results from the three calculations are close (delG=0.46, -1.09,
0.30, expt=-0.51, all in kcal/mol). So among these 3 calculations, is one
of them most "correct" or preferred? Is it right that the first two
calculations gave out rather similar DV/DL values and big rms?
Thanks a lot!!!
Victor
On Sun, Dec 11, 2011 at 11:07 AM, Victor Ma <victordsmagift.gmail.com>wrote:
> Dr. Steinbrecher
>
> Thanks a lot for your detailed explanation. It certainly helps to clarify
> some of my understanding of the TI calculations. Appreciate it.
>
>
> Victor
>
>
> On Sat, Dec 10, 2011 at 5:14 AM, <steinbrt.rci.rutgers.edu> wrote:
>
>> Hi Victor
>>
>> > This is my mdin_min_v0_l05 file:
>> > ................
>> > ifsc=1, crgmask='',scmask=':REF.A1',
>> > .................
>> > ifsc=1, crgmask='',scmask=':NEW.B1,B2',
>>
>> yes, that is what I meant. Be careful though, now all atoms except A1, B1,
>> B2 need to have identical starting positions in both processes and they
>> must occur in the same order in the molecule.
>>
>> > And if i'd like to do the 2-step as a comparison, I should try this:
>> > step1: (here use ref.prm for v1 and new.prm for v0)
>>
>> your step two looks ok, but there need to be two separate charging steps.
>> Check out the table at:
>>
>> http://ambermd.org/tutorials/advanced/tutorial9/setup.html
>>
>> for an example of this type. Only one of the runs would use softcore
>> potentials, the first and third are linear coupled between two different
>> charge states only.
>>
>> > I hope I get the direction right. Correct me if I'm wrong. Thanks a lot.
>>
>> The directions of each step dont matter, as long as you sum up the deltaGs
>> correctly. The important thing is that the sum of all steps needs to be
>> exactly your overall transformation, e.g. all changes in potential
>> function are explicitly considered.
>>
>> Kind Regards,
>>
>> Dr. Thomas Steinbrecher
>> formerly at the
>> BioMaps Institute
>> Rutgers University
>> 610 Taylor Rd.
>> Piscataway, NJ 08854
>>
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>>
>
>
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Received on Fri Dec 16 2011 - 09:30:04 PST
