# In-Silico Characterization of von Willebrand Factor Bound to FVIII
## 3 Results
### Interface Analysis
The highest Q/R value was associated to heavy chain of FL-FVIII, because FL-FVIII includes the aminoacids of B domain. In fact, the differences in IAR can be accounted to different length of protein chains in contact with the ligand, the VWF. \begin{table}
\begin{tabular}{c c c c c} \hline  & **Protein Residues** & **Interface Residues** & **ASA**, \(\mathrm{\AA^{2}}\) & \(\mathrm{\Delta G_{solv}}\)**, kcal/mol (Per Residue)** \\ \hline
**MON H (heavy chain)** & 1312 & 1283 & 66,894.3 & \(-881.3\) (\(-0.67\)) \\
**MON L (light chain)** & 644 & 627 & 33,987.6 & \(-567.8\) (\(-0.88\)) \\
**MON V (ligand VWF)** & 428 & 407 & 23,645.2 & \(-370.7\) (\(-0.87\)) \\ \hline \multicolumn{5}{c}{**INTERFACE H-L**} \\ \hline
**INTERACTING RESIDUES, MON H** & & 83 \\
**INTERACTING RESIDUES, MON L** & & 91 \\
**INTERFACE AREA, \(\mathrm{\AA^{2}}\) (per interacting residue)** & & 3039 (17.5) \\
**\(\mathrm{\Delta\Delta Gsolv}\), kcal/mol (per interacting residue)** & & \(-43.8\) (\(-0.25\)) \\ \hline
**INTERFACE H (B domain)-V** & & \\ \hline
**INTERACTING RESIDUES, MON H** & 47 \\
**INTERACTING RESIDUES, MON V** & 49 \\
**INTERFACE AREA, \(\mathrm{\AA^{2}}\) (per interacting residue)** & & 1496.3 (15.59) \\
**\(\mathrm{\Delta\Delta Gsolv}\), kcal/mol (per interacting residue)** & & \(-14.3\) (\(-0.15\)) \\ \hline \end{tabular}
\end{table} 
Table 4: **PISA results for the VWF/FL-FVIII complex. Values within brackets refer to the value specific per residue. Accessible surface area (ASA) of interface (\(\mathrm{\AA^{2}}\)). ** \begin{table}
\begin{tabular}{c c c c} \hline  & **Protein Residues** & **Interface Residues** & **ASA**, \(\mathrm{\AA^{2}}\) & \(\mathrm{\Delta G_{solv}}\)**, kcal/mol (Per Residue)** \\ \hline
**MON H (heavy chain)** & 585 & 522 & 25,123.4 & \(-610.6\) (\(-1.04\)) \\
**MON L (light chain)** & 615 & 548 & 28,830.8 & \(-636.5\) (\(-1.04\)) \\
**MON C (ligand VWF)** & 478 & 461 & 26,423.4 & \(-567.8\) (\(-1.19\)) \\ \hline \multicolumn{5}{c}{**INTERFACE H-L**} \\ \hline
**INTERACTING RESIDUES, MON H** & & 90 \\
**INTERACTING RESIDUES, MON L** & & 82 \\
**INTERFACE AREA, \(\mathrm{\AA^{2}}\) (per interacting residue)** & & 3049.4 (17.7) \\
**\(\mathrm{\Delta\Delta Gsolv}\), kcal/mol (per interacting residue)** & & \(-29.0\) (\(-0.17\)) \\ \hline
**INTERFACE L-V** & & \\ \hline
**INTERACTING RESIDUES, MON L** & & 67 \\
**INTERACTING RESIDUES, MON V** & & 72 \\
**INTERFACE AREA, \(\mathrm{\AA^{2}}\) (per interacting residue)** & & 2443.6 (17.58) \\
**\(\mathrm{\Delta\Delta Gsolv}\), kcal/mol (per interacting residue)** & & \(-26.8\) (\(-0.19\)) \\ \hline \end{tabular}
\end{table} 
Table 5: **PISA results for \(\mathrm{\acute{e}anesoctocog\ alfa}\). Values within brackets refer to the value specific per residue. Accessible surface area (ASA) of interface (\(\mathrm{\AA^{2}}\)). **The PCN analysis, as regards the topology of heavy/light chain interface (_H:L_), shows that the number of residues involved into active links between heavy and light chains was higher for the FL-FVIII, compared to the BDD-FVIII and the atomic model of \(\acute{\text{e}}\)fanesoctocog alfa. This result diverges from PISA output, but PCN and PISA reside on two different methods. However, the \"absolute interface energy\" \(\mathbf{E}_{A_{i}A_{j}}\) at heavy/light (_H:L_) chain interface was higher (more favorable) in the VWF/FL-FVIII (81.07 a.u. ), compared to values of the VWF/BDD-FVIII (40.49 a.u.) and \(\acute{\text{e}}\)fanesoctocog alfa (42.89 a.u.) complexes. This trend of energy values, calculated with PCN, are in accordance with interface energy values calculated with PISA. Moreover, the \"absolute interface energy\" \(\mathbf{E}_{A_{i}A_{j}}\) is proportional to the average inter-chain degree, which was greater at _H:L_ interface of FL-FVIII, compared to other VWF/FVIII complexes. Looking at FVIII /VWF interface, the values of \"absolute interface energy\" \(\mathbf{E}_{A_{i}A_{j}}\) were higher (more favorable) for the \(\acute{\text{e}}\)fanesoctocog alfa (31.20 a.u.) and BDD-FVIII (28.92 a.u. ), compared to FL-FVIII (22.66 a.u.