Concentration-dependent effects from the permeation enhancers capric acid and SNAC on peptide permeability: coarse-grained MD topologies, input files, and analysis code

<blockquote><p dir="ltr">This dataset supports the study "Concentration-dependent effects from the permeation enhancers capric acid and SNAC on peptide permeability." Using coarse-grained (Martini 2.2) molecular dynamics simulations in GROMACS, we investigated how two medium-chain-fatty-acid-based permeation enhancers — capric acid (C10) and salcaprozate sodium (SNAC) — partition into POPC and POPC–cholesterol (70:30) bilayers, how they alter membrane structural and dynamic properties, and how they modulate the membrane permeability of three model peptide drugs (octreotide, desmopressin, and triptorelin).

Effective permeabilities were obtained from umbrella-sampling potentials of mean force via the inhomogeneous solubility–diffusion model.</p><p dir="ltr">The archive provides everything needed to reproduce the simulations and analyses:<br>• <b>topologies/</b> — Martini 2.2 coarse-grained topologies for the force field, POPC and cholesterol, the neutral forms of capric acid and SNAC, and the three peptides.<br>• <b>mdp_files/</b> — GROMACS parameter files for the full free-energy workflow (energy minimization, equilibration, steered pulling to generate umbrella windows, and umbrella-sampling production).<br>• <b>example_system/</b> — a complete, ready-to-run built system (octreotide in a POPC–cholesterol bilayer with water and ions) with its topology and included parameter files.<br>• <b>analysis_code/</b> — Python and Bash scripts to compute effective permeabilities (D(z), R(z), Peff from WHAM PMFs and integrated autocorrelation times), assess PMF convergence, and quantify membrane properties (area per lipid, thickness, lipid-tail order parameters, flip-flop rates, enhancer incorporation, and fractional interaction matrices).<br>• <b>figure_source_data/</b> — Excel workbooks containing the numerical source data behind each main figure, including per-replicate PMF profiles and effective permeabilities with standard deviations.</p><p dir="ltr">All simulations were performed at 310.15 K with semi-isotropic pressure coupling.