Hey Basam,
I think you have to assign ionization
states and position hydrogens in your enzyme structure (typically from a
crystal structure) before you start your work.
Hydrogen atoms are required for all-atom molecular mechanics, dynamics or
electrostatic calculations. Unfortunately, most macromolecular crystal
structures contain little or no hydrogen coordinate data due to limited
resolution yet the hydrogen bond network and ionization state of titratable
groups can have a dramatic effect on simulations results.
The addition of hydrogen atoms to a macromolecule is a non-trivial task;
generally, one must determine
-
the rotamers of -SH -OH -CH3 and -NH3 groups in CYS, SER, TYR, THR, MET and LYS;
-
the ionization states of acids and bases in ARG, ASP, GLU, LYS, HIS;
-
the tautomers of imidazoles (HIS) and carboxylic acids (ASP,GLU);
-
the protonation state of metal ligand atoms CYS, HIS, ASP, GLU, etc.;
-
the ionization state of metals.
- Additionally, the element identities in HIS, terminal amides (ASN,GLN)
are often uncertain.
Therefore, protonation states from a discrete
collection of states should be preformed by optimizing the titration free energy
of all titratable
groups in the context of an all-atom model of a macromolecular structure
(including ligands and solvent). I think that MOE program can do this task
proffessionally.
Cheers,
Morad
--- On Tue, 2/16/10, Basma Ghazal
basmaghazal|a|ymail.com <owner-chemistry_-_ccl.net>
wrote:
From: Basma Ghazal
basmaghazal|a|ymail.com <owner-chemistry_-_ccl.net>
Subject: CCL: A
charge on my enzyme
To: "El-Hendawy, Morad Metwally "
<m80elhendawy_-_yahoo.com>
Date: Tuesday, February 16, 2010, 12:18
PM
Dear CCL'ers,
After
preparation of the enzyme there is a charge on it.
First: What is
the real cause of this charge? I think it is a broken residue or mutation, but I
do not know how to fix this problem.
Second: How to
deal with this charge it must be have bad effect on my results of
docking?
I will be
pleased any explanation.
Regards,
|