CycPeptMPDB-4D: Multi-Solvent Conformational Ensembles for Predicting Cyclic Peptide Permeability

CycPeptMPDB-4D: A Conformational Dynamics Dataset of Cyclic Peptides for Membrane Permeability Prediction CycPeptMPDB-4D is a large-scale structural dynamics dataset featuring atomistic molecular dynamics (MD) trajectories and 3D conformational ensembles for 5,160 structurally diverse cyclic peptides. It extends CycPeptMPDB by adding MD-derived conformations and physics-based molecular descriptors. This resource is designed to support the development of 3D and 4D (trajectory- or ensemble-based) deep learning models for predicting membrane permeability, bridging the gap between static 2D representations and the physical mechanisms of peptide–membrane interaction. A key feature of this dataset is the inclusion of simulations in both explicit water and hexane environments. This dual-solvent approach captures the "chameleon-like" behavior of cyclic peptides—their ability to adopt distinct conformational states to maximize stability in aqueous environments and minimize polar exposure in hydrophobic membrane cores. More details can be found here: (Link to be added upon publication) Dataset Structure The data is organized into solvent-specific directories containing structural information and a central metadata file: CycPeptMPDB-4D/├── Water/ 5,160 peptides│ ├── Trajectories/ *.pdb (100 frames per peptide)│ ├── Structures/ Representative conformations from clustering│ └── Logs/ Clustering analysis logs├── Hexane/ 5,160 peptides│ ├── Trajectories/ *.pdb (100 frames per peptide)│ ├── Structures/ Representative conformations from clustering│ └── Logs/ Clustering analysis logs├── CHCl3/ 6 peptides└── CycPeptMPDB-4D.csv metadata & molecular descriptors Data File and Column Descriptions The main metadata file, CycPeptMPDB-4D.csv, provides experimental permeability values (PAMPA) alongside physics-based descriptors derived from the MD trajectories. Column Description CycPeptMPDB_ID Unique identifier from the original CycPeptMPDB, inherited from CycPeptMPDB Source Reference literature for the peptide data, inherited from CycPeptMPDB Original_Name_in_Source_Literature Original peptide designation in the source literature, inherited from CycPeptMPDB Structurally_Unique_ID Identifier grouping structurally identical peptides across sources, inherited from CycPeptMPDB PAMPA Experimental membrane permeability (log cm/s), mesured by PAMPA Monomer_Length Total number of amino residues in the peptide Monomer_Length_in_Main_Chain Number of amino residues in the main-chain cycle (differs from Monomer_Length for lariat-shaped peptides) Molecule_Shape Structural topology (Circle or Lariat) Water_avgRMSD_All Average RMSD of all heavy atoms in water simulation (nm) Water_avgRMSD_BackBone Average RMSD of backbone heavy atoms in water (nm) Hexane_avgRMSD_All Average RMSD of all heavy atoms in hexane simulation (nm) Hexane_avgRMSD_BackBone Average RMSD of backbone heavy atoms in hexane (nm) Desolvation_Free_Energy Computed desolvation free energy via MMPBSA (kcal/mol) Water_3D_SASA Solvent Accessible Surface Area in water (nm²) Water_3D_PSA Polar Surface Area in water (nm²) Water_3D_NPSA Non-Polar Surface Area in water (nm²) Hexane_3D_SASA Solvent Accessible Surface Area in hexane (nm²) Hexane_3D_PSA Polar Surface Area in hexane (nm²) Hexane_3D_NPSA Non-Polar Surface Area in hexane (nm²)