Hello to all the experts of this field,
I wanted to know opinion of the expert to calculate the binding energy of
Fucose sugar in a sugar binding protein. I wanted to go for thermodynamic
integration because we have tried some other type of methods in such type of
system and results are not so precise. I have already gone through the
tutorial TUTORIAL A9: Thermodynamic Integration using soft core potentials
by By Thomas Steinbrecher. In this tutorial they discussed how calculate
relative binding free energy of two ligands (benzene and phemol) bound to a
lysozyme mutant. in three steps (removing charge on BNZ H6; changing BNZ
into PHN; adding charges on PHN O1,H6). Values of lambda used by authors is
1 to 9 and in this way they are able to get the relative binding energy of
phenol w.r.t benzene.
I am interested in binding energy of the benzene with a t4_lysozyme exactly
in same fashion. may the way to transform benzene in phenol (removing charge
on BNZ H6; changing BNZ into PHN; adding charges on PHN O1,H6) used in
tutorial, be applied for this? If I remove all the atoms of benzene in the
2nd step of transformation in fallowing way-
four states are -
A = benzene bound with T4_lysozyme in water medium
B = T4_lysozyme (benzene deleted) in water medium
C = benzene in water medium
D = water medium only.
Process 0 (V0) * prmtop: t4_bnz
* crgmask=':BNZ.C1
,C2,C3,C4,C5,C6,H1,H2,H3,H4,H5,H6'
*
scmask=':C1,C2,C3,C4,C5,C6,H1,H2,H3,H4,H5,H6'
* ifsc=1
Process 1 (V1) * prmtop: t4_phn
* crgmask=''
* scmask= ''
* ifsc=1
So we are removing whole benzene ring from the structure, and now there is
noting to do in the step 3rd (like in tutorial adding charges on PHN O1,H6)
because all the benzene is now absent. Definitely I need to do TI
calculation only in solvent molecules to maintain the cycle so could it
cause the problem too ?? Will this calculation give me the binding energy of
benzene in t4_lysozyme ?? If someone have other idea to calculate the
binding energy of benzene with t4_lysozyme using TI approach, please discuss
it with me.
Thanking You
Sushil
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Received on Thu Jan 14 2010 - 09:00:02 PST
