Quantitative Structure–Property Relationship Modeling of Diverse Materials Properties

Quantitative Structure–Property Relationship Modeling of Diverse Materials Propertie

The computational model of the complex superimposed on the B and C chains of the X-ray crystal structure (BCxray).

<p>The G3 chains of the model and BCxray are in yellow and cyan, respectively, while the HER2 chains of the model and BCxray are shown in red and green, respectively.</p

SPR binding parameters for HER2 constructs binding to the DARPin G3 and trastuzumab.

<p>Note 1: The values given are the average values for three separate measurements and the uncertainties represent one standard deviation.</p>a<p>Note 2: About 30-fold higher affinities are obtained when avoiding random amine coupling of this very small DARPin [9,36], (Nagy-Davidescu and Plückthun, unpublished).</p

LigPlot diagram of all G3 (red) - HER2 (blue) residue interactions in the model.

<p>LigPlot diagram of all G3 (red) - HER2 (blue) residue interactions in the model.</p

Structural model of the DARPin G3 (cyan) in complex with the human epidermal growth factor receptor 2 HER2 (green).

<p>In magenta the structure of trastuzumab Fab bound to HER2 is shown superimposed on the G3-HER2 complex.</p

Top ZRANKed docking solutions and their computed metrics shape complementarity (Sc) and interaction energy (IE).

a<p>This ZDOCK solution was selected as the optimal or preferred solution for the structural model of the G3 - HER2 complex.</p

SPR binding sensorgrams for the interaction of HER2 wild type and mutant proteins with immobilized DARPin G3 (left panels) and trastuzumab (right panels).

<p>Injected analyte (HER2) protein construct: wild type (A and F), Leu 525→Ala (B and G), Ser 551→Ala (C and H), Val 552→Ala (D and I) and Phe 555→Ala (E and J). Typically, injected HER 2 protein concentrations were diluted three-fold in running buffer from 81 nM to 1 nM except in B, D and E where the concentration series were diluted from 729 nM down to 9 nM. Overlayed triplicate binding responses are shown (black lines). Binding data were globally fit to a simple 1∶1 interaction model (orange lines).</p