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

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.