[gmx-users] Mutation-induced binding affinity change using BAR

Justin Lemkul jalemkul at vt.edu
Wed Dec 19 14:19:20 CET 2012

On 12/19/12 5:29 AM, Oliver Kuhn wrote:
> Hi Gromacs People,
> we want to do a BAR calculation to calculate the binding affinity change
> induced by a mutation.
> That means:
> - We want to transform a residue from aminoacid1 (aa1) to aminoacid2 (aa2)
> in a single-transformation approach (transforming both vdw and coulomb at
> the same time)
> lambda=0 :  aa1 switched on and aa2 switched off
> lambda=1 :  aa1 switched off and aa2 switched on
> - to calculate binding free energy, we would calculate this transformation
> process once in the complex and once in the receptor and calculate the
> difference
> However, I can find no information how to have both aminoacids switched on
> half, for example for lambda=0.5
> Any tutorials I found decouple atoms from its environment but not with
> switching on different atoms at the same time.
> In Amber, this is possible by using two topologies.
> Is this possible with Gromacs and where can I read how to do it?

The dual topology approach is discussed in manual section 5.7.4.


> A simpler example illustration the problem would be:
> Transforming Toluene (Benzol-CH3) to Phenole (Benzol-OH) in water (to
> calculate the change in solvation energy)
> from lambda 0 to 1, -CH3 interactions should be gradually switched off and
> -OH switched on (with both switched on half at lambda=0.5)
> For further disambiguition:
> We want to perform equilibrium simulations at discrete lambda steps (with
> delta_lambda=0 for each simulation) - no slow growth
> Any help is greatly appreciated.
> Greets
> Oliver


Justin A. Lemkul, Ph.D.
Research Scientist
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080


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