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
Received on Mon May 13 2013 - 08:00:02 PDT
