Table 2B.
Calculated changes in thermodynamic stability and other protein properties of Fv portion of MAB 1 due to single point mutations*
| MAB 1 variant | ΔΔGFv (Kcal/mole) | ΔpIFv | ΔZFv-net | ΔZFv-app | ΔξFv (mV) | ΔPagg-LC |
|---|---|---|---|---|---|---|
| M2 (E59R) | −2.33 | 1.14 | 2.04 | 0.67 | 6.94 | 0.02 |
| M3 (E59Y) | −2.34 | 0.18 | 1.15 | 0.38 | 3.91 | 0 |
| M4 (E59K) | −1.75 | 1.12 | 2.03 | 0.67 | 6.93 | 0.02 |
| M5 (L45K) | 1.99 | 0.40 | 0.97 | 0.32 | 3.32 | −3.56 |
| M6 (V44K) | 0.48 | 0.37 | 1.12 | 0.37 | 3.81 | −3.85 |
*
To compute these changes, ResidueScan module in MOE2013.08 was utilized. All variants were evaluated using conformational ensembles generated from 1 nanosecond implicit solvent molecular dynamics simulations. See Materials and Methods for details. Not that all the calculations are limited to the Fv portions of the MAB 1 and variants only. For a given property X, the change in property was computed as follows: ΔX = Xvariant Fv – XM1 Fv, where X is free energy, pI, net or apparent charge, ξ-potential or aggregation propensity.