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Comment on the calculations in protein thermodynamics

Open AccessPublished:April 06, 2018DOI:https://doi.org/10.1074/jbc.L118.002358
      We found a recent paper (
      • Mukherjee S.
      • Griffin D.H.
      • Horn J.R.
      • Rizk S.S.
      • Nocula-Lugowska M.
      • Malmqvist M.
      • Kim S.S.
      • Kossiakoff A.A.
      Engineered synthetic antibodies as probes to quantify the energetic contributions of ligand binding to conformational changes in proteins.
      ) that would be valuable in the field of protein thermodynamics. However, the paper contains some calculation errors. Here, we discuss the errors. Following the notations in Table 2 of the paper, the ensuing relationship of entropy can be established.
      TΔS0Maltose: MBP + TΔS0MBP: sAB-11M in 1 mm maltose = TΔS0MBP: sAB-11M + TΔS0Maltose: MBP in 5-fold molar excess sAB-11M. Plugging the corresponding values reported in Table 2 of the paper to the equation does not satisfy the equality: 10.4 + (−2.0) ≠ 5.6 + 2.0 (in kcal/mol).
      Secondly, there are errors made in the calculation of ΔG0 in Table 2. Based on the equation, ΔG0 = ΔH0TΔS0 (
      • Chang R.
      Physical Chemistry for the Chemical and Biological Sciences.
      ), we found that ΔG0MBP: sAB-11M in 1 mm maltose = −14 − (−2) = −12 kcal/mol, not −11.4 kcal/mol as stated in the paper.ΔG0Maltose: MBP in 5-molar excess of sAB-11M = −8.9 − 2 = −10.9 kcal/mol, not −11.1 kcal/mol. ΔG0Maltose: MBP in 5-molar excess of sAB-P1 = −14 − (−1.0) = −13 kcal/mol, not −12.6 kcal/mol.
      The third error we found is with KD for the binding of MBP to sAB-P1 in 1 mm maltose in Table 2: KD = exp (ΔG0/RT) = exp(−11,000 cal/mol × 4.184J/cal/(8.314 J/mol K × 298.15 K)) = 8.6 nm, not 0.9 nm as in the paper. Lastly, Kmal and KsAB in Fig. 5 are 0.83 × 10−6 m and 0.47 × 10−6 m, not 0.83 × 10−3 m and 0.47 × 10−3 m, respectively.

      References

        • Mukherjee S.
        • Griffin D.H.
        • Horn J.R.
        • Rizk S.S.
        • Nocula-Lugowska M.
        • Malmqvist M.
        • Kim S.S.
        • Kossiakoff A.A.
        Engineered synthetic antibodies as probes to quantify the energetic contributions of ligand binding to conformational changes in proteins.
        J. Biol. Chem. 2018; 293 (29321208): 2815-2828
        • Chang R.
        Physical Chemistry for the Chemical and Biological Sciences.
        University Science Books, Sausalito, CA2000