Hi Everyone,
I am attempting to calculate substrate binding free energy using
Thermodynamic Integration in Amber11.
I have minimised, equilibrated and run NPT (2 ns) for the solvated enzyme
in the substrate bound and unbound states. I was planning to conduct TI
simulations for 12 windows for the system. From my reading of the amber 11
manual the procedure needs to be the following....
With the output of the 2ns (using the .top and .rst files from) enzyme
simulation of the substrate bound state;
A. Phase out Electrostatic interactions first.
Run 12 simulations (each with a different lambda value) and include the
substrate atoms in the crgmask flag in the md.in file, while setting ifsc=0.
B.Then Phase out VDW interactions.
Again run 12 simulations (each with a different lambda value) and set
ifsc=1 and include the substrate atoms in the scmask flag in the
md.infile, while setting crgmask="".
I have the following questions about the procedure....
1. Is my understanding of the procedure correct?
2. Will my .top & .crd files be the same for both sets of simulations? It
is my understanding that I need to use the same .top that I used for the
substrate bound NPT simulation and the .rst file that I obtained from the
NPT run will become my .crd file.
3. Do I need to perform simulations that involve phasing out the substrate
(alone) in a solvated environment?
I have followed the tutorial available online (
http://ambermd.org/tutorials/advanced/tutorial9/ and
http://ringo.ams.sunysb.edu/index.php/AMBER_TI_Tutorials) but I still seem
to have a somewhat unclear understanding of how to proceed.
I will be grateful for any advise that I get.
--
Vivek S. Bharadwaj
Graduate Student
Department of Chemical and Biological Engg.
Colorado School of Mines
Golden Colorado
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Received on Tue Sep 25 2012 - 13:00:04 PDT
