CycPeptMPDB-4D: Multi-Solvent Conformational Ensembles for Predicting Cyclic Peptide Permeability
Authors/Creators
-
1.
Agency for Science, Technology and Research
-
2.
National University of Singapore
-
3.
Nanyang Technological University
-
4.
Singapore Eye Research Institute
Description
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) |