Consistency of interface DDG calculations

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    • #1861

        Hello, I have been trying to validate interface energies computed using Rosetta 2.3, but have been having some difficulty obtaining agreement between two expressions that should be equivalent.

        I start with a protein with two chains in a single PDB file, ab.pdb.

        Then I run Rosetta++ with the following flags:
        -interface -ddg_bind_only -s ab.pdb -intout ab.txt -output_structure -Wpack_only -relax_unbound false

        This gives me three files:
        ab_nat_0001.pdb (A chain only)
        ab_nat_0002.pdb (B chain only)
        ab_nat_0003.pdb (A+B chains together)

        along with the following energies:
        dG = E(AB) – E(A) – E(B) = (1253.7) – (672.7) – (639.4) = -58.4 final dG

        Then I take each of the ab_nat_000*.pdb files, and rescore them using the following flags:
        -s ab_nat_0001.pdb -score -fa_input -intout score.txt -overwrite -scorefile a.score

        This time I obtain
        E(AB) – E(A) – E(B) = (1253.7) – (669.5) – (634.4) = -50.3

        which is different by 8 kcal/mol, because the energies of A and B are now different when scored separately.

        The inconsistency persists despite trying many changes:
        — using softened potentials
        — relaxing structure beforehand
        — setting relax_unbound to false

        Does anyone have any idea what could be causing these energy differences? Thanks!

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