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From: Victor Ma <victordsmagift.gmail.com>

Date: Fri, 16 Dec 2011 11:23:30 -0600

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
*

*>>
*

*>> _______________________________________________
*

*>> AMBER mailing list
*

*>> AMBER.ambermd.org
*

*>> http://lists.ambermd.org/mailman/listinfo/amber
*

*>>
*

*>
*

*>
*

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Received on Fri Dec 16 2011 - 09:30:04 PST

Date: Fri, 16 Dec 2011 11:23:30 -0600

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:

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Received on Fri Dec 16 2011 - 09:30:04 PST

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