DOI: 10.5281/zenodo.18754429
title: CycPeptMPDB-4D: Multi-Solvent Conformational Ensembles for Predicting Cyclic Peptide Permeability

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 (e.g., Circle, Lariat).


Water_avgRMSD_All
Average RMSD of all atoms in water simulation (nm).


Water_avgRMSD_BackBone
Average RMSD of backbone atoms in water (nm), excluding H.


Hexane_avgRMSD_All
Average RMSD of all atoms in hexane simulation (nm).


Hexane_avgRMSD_BackBone
Average RMSD of backbone atoms in hexane (nm), excluding H.


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).