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\title{Supplementary Information: Inhibition of mutant RAS-RAF interaction by mimicking structural and dynamic properties of phosphorylated RAS}
\author[1,\authfn{1},\authfn{2}]{Metehan Ilter}
\author[2,3,\authfn{2}]{Ramazan Ka\c{s}mer}
\author[4,\authfn{3}]{Farzaneh Jalalypour}
\author[4]{Canan Atilgan}
\author[2]{Ozan Topcu}
\author[2,5,*]{Nihal Karaka\c{s}}
\author[6,7,*]{Ozge Sensoy}
\affil[1]{Graduate School of Engineering and Natural Sciences, Istanbul Medipol University, Istanbul, Turkey}
\affil[2]{Cancer Research Center, Institute for Health Sciences and Technologies (SABITA), İstanbul Medipol University, İstanbul, Tukey}
\affil[3]{Medical Biology and Genetics Program, Graduate School for Health Sciences, Istanbul Medipol University, Istanbul Turkey}
\affil[4]{Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey }
\affil[5]{Department of Medical Biology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey }
\affil[6]{Department of Computer Engineering, School of Engineering and Natural Sciences, Istanbul Medipol University, Istanbul, Turkey}
\affil[7]{Regenerative and Restorative Medicine Research Center (REMER), Institute for Health Sciences and Technologies (SABITA), İstanbul Medipol University, İstanbul. Turkey}
\corr{nkarakas@medipol.edu.tr}{NK}
\corr{osensoy@medipol.edu.tr}{OS}

\contrib[\authfn{2}]{These authors contributed equally to this work}


\presentadd[\authfn{1}]{Molecular Simulations and Design Group, Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany}
\presentadd[\authfn{3}]{Department of Applied Physics, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden}
%\affil[5]{Department of Medical Biology, School of Medicine, İstanbul Medipol University, İstanbul 34810, Turkey.}
\captionsetup{labelformat=empty}

\begin{document}
\maketitle
%\newpage
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\begin{table}[ht!]
  \renewcommand\thetable{Supplementary file 1a}
  \caption{\textbf{Supplementary file 1a} The average number of water molecules within 5 \AA\ of GTP  were calculated over the course of the ligand-bound HRAS\textsuperscript{G12D} systems.}
\centering
  \begin{tabular}{llll}
    \hline
    Ligand-bound H-RAS\textsuperscript{G12D}  & $\mu$\textsubscript{water} \\
    \hline
    Cerubidine               & 119.1{$\pm$}0.3  \\
    Tranilast   & 104.5 {$\pm$}0.4 \\
    Nilotinib               & 95.3	 {$\pm$}0.5\\
    Epirubicin               & 106.2 {$\pm$}0.4  \\
    \hline
  \end{tabular}
   \label{tblS2}
\end{table}
\begin{table}[ht!]
  \renewcommand\thetable{Supplementary file 1b}

  \caption{\textbf{Supplementary file 1b} Total simulation time performed for ligand- HRAS\textsuperscript{G12D} complexes and changes in the backbone RMSF profiles of  cerubidine-, tranilast-, nilotinib-, and epirubicin-bound HRAS\textsuperscript{G12D} systems with respect to those of HRAS\textsuperscript{G12D}.}
\centering
  \begin{tabular}{lllll}
    \hline
    Ligand  & Duration (ns) & $\Delta$RMSF(Y32) (\AA) & $\mu$\textsubscript{$\Delta$RMSF(RAF-RBD)} (\AA) & $\mu$\textsubscript{$\Delta$RMSF(RAF-CRD)} (\AA) \\
    \hline
    Cerubidine    & 3069 & 1.2 $\pm$ 0.3 & 1.5 $\pm$ 0.4 & 0.2 $\pm$ 0.1\\
    Tranilast     & 3705 & 1.2 $\pm$ 0.5 & 1.2 $\pm$ 0.7 & 0.4 $\pm$ 0.2\\
    Nilotinib     & 3053 & 1.7 $\pm$ 0.7 & 1.9 $\pm$ 0.8 & 0.4 $\pm$ 0.2\\
    Epirubicin    & 2884 & 2.3 $\pm$ 0.5 & 2.0 $\pm$ 0.8 & 0.3 $\pm$ 0.2\\    \hline
  \end{tabular}
   \label{tblS1}
\end{table}
\begin{table}[ht!]
  \renewcommand\thetable{Supplementary file 1c}

  \caption{\textbf{Supplementary file 1c} The results of PRS calculations for the transition between initial and target states.}
  \centering
  \scalebox{0.80}{
\begin{tabular}{cccccc}
  \toprule
  Ligand     & State & D12-P34 (\AA) & G60-GTP (\AA) & PRS selected residues & PRS overlap\textit{(O\textsuperscript{i}})   \\
  \midrule
      Nilotinib & Target state-1    & 22.4 (open) & 5.1 (closed) &  34, 35, 33, 37, 32, 36 & 0.70-0.62 \\
            & Target state-2    & 15.3 (partially open) & 12.7 (open) & 61, 62, 63, 23, 22, 65 & 0.57-0.51  \\
            & Target state-3   & 22.6 (open) & 19.8 (open) & 34, 35, 33, 37, 36, 66 & 0.66-0.59 \\
  \addlinespace
  Tranilast  & Target state-1   & 27.0 (open) & 9.1 (closed) & 32, 36, 33, 37, 34, 35 & 0.74-0.67  \\
            & Target state-2   & 14.8 (partially opened) & 12.3 (open) & 22, 18, 23, 104, 87, 6 & 0.55-0.54  \\
            & Target state-3    & 20.1 (open) & 14.8 (open) & 34, 33, 35, 32, 37 & 0.54-0.50 \\
              \addlinespace
  Epirubicin  & Target state-1   & 29.0 (open) & 7.7 (closed) & 32, 33, 34, 35, 37, 36 & 0.61-0.51  \\
            & Target state-2   & 13.3 (partially opened) & 17.8 (open) & 63,62 & 0.51-0.50   \\
            & Target state-3    & 22.0 (open) & 15.2 (open) & 34, 35, 33, 37, 36, 66 & 0.61-0.59  \\
  \bottomrule
\end{tabular}}
   \label{tblS5}
\end{table}
\end{document}