Dear Thomas,
The H->OMe mutation (B->C) seems to have a problem representing a change of
two states which may have bigger difference in configurational space. Can
you check if equilibration has been reached for this instead for A->B; is
there any way to check also DDG convergence for that step? In this way you
will see if extra simulation is needed?
-----Original Message-----
From: Thomas Exner [mailto:thomas.exner.uni-konstanz.de]
Sent: Monday, May 13, 2013 5:48 PM
To: AMBER Mailing List
Subject: [AMBER] Inconsistent results for TI calculations
Dear AMBER users:
I have some strange results in my TI calculations and hope that somebody can
help me in figuring out what goes wrong. I adapted the amber TI tutorial for
my calculation on three different ligands. First I did the simulation A->B
changed an OH group to a single proton. In the A->C simulation the same OH
group was transformed to a OMe group. Finally I did the B->C transformation.
The resulting energies are as follows:
A->B: -0.57
A->C: +0.82
B->C: -8.96
Adding the two first simulations together ends in a free energy difference
of +1.39 kcal/mol and predicts B to be the better binder than C. in the
direct simulation C is much stronger binding. To test if there are some
problems with the equilibration phase, I run the first simulation for
additional 3ns, but the results are very similar for each ns separately.
Additionally, I tested with the last simulation (since there the structure
changes the strongest) if additional lambda points would help. But going
from lambda changing by 0.1 to 0.05 also did not change the result
dramatically. I also looked at the structures and they all look very similar
and reasonable. Does anyone have an idea what I can do to find reasons for
these inconsistent results?
Thank you very much.
Thomas
--
____________________________________________________________________________
____
Dr. Thomas E. Exner
Theoretische Pharmazeutische Chemie & Biophysik Lehrstuhl Pharmazeutische
Chemie Pharmazeutisches Institut Eberhard Karls Universität Tübingen Auf der
Morgenstelle 8 (Haus B)
72076 Tübingen
Germany
Tel.: +49-(0)7071-2976969
Mobil: +49-(0)171-3807485
Fax: +49-(0)7071-295637
E-Mail: Thomas.Exner[at]uni-tuebingen.de
Fachbereich Chemie und Zukunftskolleg
Universität Konstanz
78457 Konstanz
Germany
Tel.: +49-(0)7531-882015
Fax: +49-(0)7531-883587
E-Mail: Thomas.Exner[at]uni-konstanz.de
____________________________________________________________________________
____
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Mon May 13 2013 - 10:00:03 PDT
