Exploring Protein-Peptide Recognition Pathways Using a Supervised Molecular Dynamics Approach  Veronica Salmaso, Mattia Sturlese, Alberto Cuzzolin, Stefano Moro  Structure  Volume 25, Issue 4, Pages 655-662.e2 (April 2017) DOI: 10.1016/j.str.2017.02.009 Copyright © 2017 Elsevier Ltd Terms and Conditions

Structure 2017 25, 655-662.e2DOI: (10.1016/j.str.2017.02.009) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 1 Bcl-XL-BAD Recognition Pathway (A) Superimposition between the experimental nuclear magnetic resonance complex (PDB: 1G5J) (orange-colored BAD peptide) and the pepSuMD conformation with lowest RMSD along the trajectory (blue-colored BAD peptide). The superposition was performed considering only the target protein residues. The peptide is shown using a ribbon style while, the protein is represented using both ribbon (gray) and surface (white, transparent rendering). The nomenclature of the most relevant Bcl-XL helices is reported on the corresponding α helix segment. (B) RMSD of simulated BAD peptide Cα carbon atoms against PDB references. (C) Interaction energy landscape. (D) Peptide-target recognition map. (E and F) Dynamic electrostatic interaction energy, on the peptide and protein side, respectively. Structure 2017 25, 655-662.e2DOI: (10.1016/j.str.2017.02.009) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 2 MDM2/p53 Recognition Pathway (A) Superimposition between the experimental crystallographic complex (PDB: 1YCQ) (orange-colored p53 peptide) and the pepSuMD conformation with lowest RMSD along the trajectory (blue-colored p53 peptide). The superposition was performed considering only the target protein residues. The protein structure is represented using both ribbon (gray) and surface (white, transparent rendering). The peptide is represented using the ribbon style and the most relevant residues for the interaction, Phe19, and Thr23, are also rendered by heavy atoms, the carbon atoms of which are colored according to the corresponding ribbon. (B) RMSD of simulated p53 peptide Cα carbon atoms against PDB references. (C) Interaction energy landscape. (D) Peptide-target recognition map. (E and F) Dynamic electrostatic interaction energy, on the peptide and protein side, respectively. Structure 2017 25, 655-662.e2DOI: (10.1016/j.str.2017.02.009) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 3 MDM2/SAH-p53-8 Recognition Pathway (A) Superimposition between the experimental crystallographic complex (PDB: 3V3B) (orange-colored peptidomimetic) and the pepSuMD conformation with lowest RMSD along the trajectory (blue-colored peptidomimetic). The superposition was performed considering only the target protein residues. The protein is represented using both ribbon (gray) and surface (white, transparent rendering). The peptidomimetic is represented using full heavy-atom style. The position of the most relevant residues for the interaction, Phe19 and Thr23, are indicated by black arrows. (B) RMSD of simulated SAH-p53-8 ligand heavy atoms against PDB references. (C) Interaction energy landscape. (D) Peptidomimetic-target recognition map. (E) Dynamic electrostatic interaction energy, on the protein side. Structure 2017 25, 655-662.e2DOI: (10.1016/j.str.2017.02.009) Copyright © 2017 Elsevier Ltd Terms and Conditions