Nitin,
See my responses below.
-Bill
On Thu, Feb 27, 2014 at 10:40 AM, Nitin Sharma <sharmanitin.nus.edu.sg>wrote:
> Dear amber users,
>
> I am confused about a small fact related to alanine scanning and energy
> decomposition. I have read the amber tutorial
> http://ambermd.org/tutorials/advanced/tutorial3/py_script/section3.htmand also read the paper MMPBSA.py: An Efficient Program for End-State Free
> Energy Calculations , J. Chem. Theory Comput. 2012, 8, 3314-3321.
>
>
> a) As mentioned in paper "Alanine scanning is an alternative to
> decomposition analysis that involves mutating a single amino acid in the
> system to alanine", "When alanine scanning is enabled, MMPBSA.py
> determines the mutated residue by comparing the original and mutant
> topology files" menaing that one is allowed to perform only one mutation
> and also that mutation site is automatically determined by the program.
>
> Now my query is it possible to do alanine scanning if my protein already
> has certain amino acid -> alanine mutation i.e Prot and Prot H->A and I
> also want to study alanine scanning by mutating a certain residue in Prot
> H->A ?
>
I am not 100% sure I know what you are asking here, but I will say that you
get to choose which residue is mutated based on the topology files you give
MMPBSA.py. When you run the alanine scanning calculation, you will provide
MMPBSA.py with both "wild-type" and alanine-mutant topology files. When you
make the alanine-mutant topology file, you will decide which residue you
want MMPBSA.py to mutate and create that topology file accordingly. So
MMPBSA.py determines which residue to mutate based on the alanine residue
in your alanine-mutant topology file that is not an alanine in your
wild-type topology file.
>
>
> b) As mentioned in the tutorial "Now before you quit tleap you should
> create the topology and coordinate files from the mutant pdb files you just
> created:" But as I have already performed MD simulation will it be ok to
> create the topology and coordinate files from the mutant pdb files with
> same leaprc file used for non-mutant pdb files or I have to run complete
> process from the scratch?
>
>
Yes, you can create the topology and coordinate files from the mutant pdb
files with the same leaprc file used for the non-mutant pdb files. The
reason this is mentioned in the tutorial is because it is advised to make
all topology/coordinate files at the same time in order to maintain
consistency among the files.
>
> c) I have observed through number of amber archives that there can
> be more inconsistency between PBSA and PBSA decomposition than in case of
> GBSA. So is it best to stick to GBSA ?
>
If you can get away with running the calculations with GBSA, I would advise
doing that.
>
>
>
> d) I will be opting for Per-residue decomposition as mentioned in
> paper that "decomposition analysis is not pairwise decomposable" and in
> Ambertools12 manual that for large number of residues pairwise can quickly
> create very large files which can slow the process. Now as my options are
> only
>
> 1 - Per-residue decomp with 1-4 terms added to internal potential terms
>
> 2 - Per-residue decomp with 1-4 EEL added to EEL and 1-4 VDWadded to
> VDWpotential terms.
>
> Can someone tell me basic difference between these two and which is better
> option?
>
>
There isn't really an option here that is better than the other one. It is
simply a way of letting you know what terms the 1-4 decomp terms will be
added to. This is just so you know what overall energy values also contain
your decomposition energies. That being said, I usually choose to run the
calculations with idecomp=2 so that the 1-4 terms are added to their
respective similar energy terms.
>
>
> Thanks and regards,
> Nitin Sharma
> Department of Pharmacy,Faculty of Science,National University of
> Singapore,block S7, Level 2, Singapore : sharmanitin.nus.edu.sg<mailto:
> sharmanitin.nus.edu.sg> ; http://www.linkedin.com/in/imsharmanitin
>
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>
--
Bill Miller III
Post-doc
University of Richmond
417-549-0952
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Received on Thu Feb 27 2014 - 12:30:04 PST
