Replicated 2-μs molecular dynamics trajectory and simulation data for de novo macrocyclic peptide-Sortase A complexes

In plain language

This computational dataset comprises molecular dynamics simulation files for three de novo-designed macrocyclic peptide binders targeting Staphylococcus aureus Sortase A. The complexes, designated SMP01, SMP41, and SMP103, were each evaluated across three independent two-microsecond all-atom simulations using GROMACS, yielding eighteen microseconds of aggregate sampling data. Deposited records include downsampled, protein-only coordinate trajectories recorded at one-hundred-picosecond intervals, final coordinate structures, input run parameters, and energy files. Associated repositories supply the necessary force-field parameters, topologies specifying head-to-tail cyclisation, and custom scripts for structural, contact-occupancy, and enhanced-sampling analyses. The data provide a reproducible basis for assessing the stability and dynamic interactions of these candidate peptide inhibitors against Sortase A without the storage footprint of solvent coordinates.

Key takeaways

The dataset provides eighteen microseconds of total molecular dynamics simulation data across three candidate macrocyclic peptide complexes with Sortase A.
Three distinct complexes, named SMP01, SMP41, and SMP103, were each simulated in triplicate for two microseconds.
Topology files explicitly encode the head-to-tail covalent cyclisation of the designed peptides.
Deposited coordinate trajectories exclude solvent and ions and are downsampled to one-hundred-picosecond intervals to facilitate public access.
Complete simulation input files, force fields, and analysis scripts are made available to support independent verification and analysis.

Why it matters

Staphylococcus aureus poses persistent therapeutic challenges, making its virulence enzymes attractive targets for intervention. This dataset provides open, fully reproducible atomistic simulation models of novel cyclic peptide designs binding to Sortase A. By providing detailed coordinates and parameters, it allows researchers to examine how cyclic peptides maintain contact with bacterial targets over extended timeframes.

Commercialisation angle

This work represents very early-stage computational discovery for potential anti-virulence or antibacterial therapeutics targeting Staphylococcus aureus. Pharmaceutical developers and computational drug-design researchers might use the data and models to refine candidate Sortase A inhibitors. However, the abstract describes only simulated computational datasets, indicating substantial laboratory synthesis and experimental validation are required before any commercial application is viable.

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Abstract

This dataset accompanies the computational study of de novo-designed macrocyclic peptide binder candidates targeting Staphylococcus aureus Sortase A (SrtA). It contains molecular dynamics trajectory and simulation data for three SrtA-macrocyclic peptide complexes: SMP01-SrtA, SMP41-SrtA, and SMP103-SrtA. For each complex, three independent 2-μs all-atom molecular dynamics simulations (Replicas 1-3) are deposited, corresponding to a total production sampling time of 6 μs per peptide–SrtA complex and 18 μs across the three designed complexes. For each replica, the following files are provided: .xtc – processed protein-only trajectory containing Sortase A and the corresponding macrocyclic peptide, spanning the complete 2-μs production simulation and sampled at 100-ps intervals. .tpr – original GROMACS production run-input file for the corresponding explicitly solvated simulation. .edr – original GROMACS energy file for the corresponding production simulation. .gro – final coordinate structure of the complete explicitly solvated system from the corresponding production simulation. Trajectory size reduction The original production trajectories contain the complete explicitly solvated systems, including Sortase A, the macrocyclic peptide, water molecules, and ions, and were written at a substantially higher temporal frequency. These full-resolution trajectories are large (approximately 20 GB or more per 2-μs simulation). To enable practical public deposition while preserving the complete temporal extent of every simulation, the deposited .xtc trajectories were generated from the original production trajectories using GROMACS. Two reductions were applied: Solvent and ions were omitted from the deposited XTC files, retaining Sortase A and the corresponding macrocyclic peptide; and The trajectories were temporally downsampled to 100-ps intervals. No truncation of the production simulations was performed. Each deposited XTC therefore spans the complete 2 μs of its corresponding replica. A 2-μs trajectory sampled at 100-ps intervals contains 20,001 coordinate frames, spanning 0 to 2,000 ns. The original full-system, full-resolution production trajectories were used for the molecular dynamics analyses reported in the associated manuscript. The processed trajectories deposited here are provided to facilitate public access, structural inspection, independent trajectory analysis, and verification of the reported simulation behavior while avoiding unnecessary storage of high-frequency solvent coordinates. The accompanying .tpr and .edr files correspond to the original explicitly solvated production systems and are retained to provide simulation provenance and access to the original production parameters and energetic information. Associated simulation inputs and analysis scripts The small, human-readable files required to inspect and reproduce the molecular dynamics setup—including starting coordinates (.pdb and .gro), GROMACS molecular topologies (.top and .itp), position-restraint files, simulation parameter files (.mdp), and the CHARMM36 force-field distribution used for system preparation and simulation, are publicly available in the associated GitHub repository: Molecular dynamics input files:https://github.com/Olanrewaju-Durojaye/Molecular-Dynamics-Input-Files-for-De-Novo-Macrocyclic-Peptide-Sortase-A-Complexes The deposited topology files explicitly encode the head-to-tail covalent cyclization of SMP01, SMP41, and SMP103, allowing independent verification that the peptides were simulated as macrocyclic rather than linear structures. Custom scripts used for structural, cross-predictor, molecular dynamics, contact-occupancy, and enhanced-sampling analyses are available separately at: Analysis scripts:https://github.com/Olanrewaju-Durojaye/Scripts_for_SMP_Project_analyses Dataset composition The Zenodo dataset contains: SrtA-SMP01 complex: three independent 2-μs production replicas SrtA-SMP41 complex: three independent 2-μs production replicas SrtA-SMP103 complex: three independent 2-μs production replicas This corresponds to nine independent production trajectories and 18 μs of aggregate production MD sampling across the three designed peptide–SrtA complexes. Simulation software: GROMACS 2026.0-dev-20250915-1e492c61b4Force field: CHARMM36 (charmm36-jul2021.ff)Water model: TIP3P Full methodological details, simulation conditions, trajectory analyses, and statistical comparisons are provided in the associated manuscript.