Free Energy couple-intramol = yes + bonded_lambdas?

Hi,

I’m using alchemical free energy changes to investigate the free energies of binding between dinucleotides. Because of their size, I’ve set couple-intramol = yes. However, I am also using bonded interactions specified in the [ intermolecular_interactions ] section of the topology file. Consequently, to add or remove restraints between the dinucleotides I am changing the value of bonded_lambdas.

The manual specifies that changing bonded_lambdas affects bonded interactions, and according to the manual bonded interactions include covalent bond stretching etc. By combining couple-intramol = yes with bonded_lambdas, am I then also affecting these interactions? I note also that the manual states this regarding couple-intramol = yes: “The intra-molecular Van der Waals and Coulomb interactions are also turned on/off” which implies this will not affect the bonding interactions (I guess it would be strange if it did because AFAIK I can’t simulate covalent bond formation or breaking without a reactive force field anyway??).

Will couple-intramol = yes affect bonded interactions intramolecularly when bonded_lambdas is turned on?

Thank you for your time.

Jack