[gmx-users] mutation to/from proline
Mark.Abraham at anu.edu.au
Tue Apr 27 16:23:30 CEST 2010
On 25/04/2010 10:18 PM, afsaneh maleki wrote:
> I want to calculate relative free energy associated to mutation of P1
> (native protein) to p2 (mutated protein).In this mutation, Isolusine (in
> P1) is mutated to Proline(in P2). With using Thermodynamic cycle:
> Bilayer+P1= = => Bilayer-P1 delta G1 (association P1)
> Bilayer+P2= = => Bilayer-P2 delta G2 (association P2)
> Where P1 = = => P2 deltaG3
> Bilayer-P1 = = = > Bilayer-P2 deltaG4
> So, delta deltaG= (delta G1(association P1)- deltaG2 (association P2))=
> (deltaG3- deltaG4)
> To define the B state that will be used for the free energy calculation.
> For this; I need to specify the new atom type of each mutated atom and
> the set of parameters to it.
> But my question is that with regarding to special structure of proline,
> is it possible to update topology file? Who was done mutation of proline
> before? I searched but I didn’t find! Or is there manual for mutating
> from/to proline?
That's a pretty significant perturbation to be trying to study, because
there have to be protein backbone rearrangements to accommodate proline,
mutation of methyl to H, and a free alkyl chain losing its entropy and a
pair of H. I expect you'll need to do a phenomenal amount of sampling to
get useful results, even if you can think of a sensible mutation
reaction coordinate. It would not surprise me if such a mutation had not
been reported in the literature.
Accordingly, you might be best served by such methods implemented for
implicit solvation in some other simulation package (if such exists).
More information about the gromacs.org_gmx-users