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.htm and 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 ?
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?
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 ?
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?
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
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Thu Feb 27 2014 - 08:00:02 PST
