REPLICATED ENHANCED-SAMPLING DATA FOR THE SMP103-SORTASE A COMPLEX

Abstract

This dataset accompanies the computational study of the de novo-designed head-to-tail macrocyclic peptide SMP103 targeting Staphylococcus aureus Sortase A (SrtA). It contains data from three independent enhanced-sampling calculations performed to characterize the energetic response associated with dissociation of SMP103 from the SrtA substrate-recognition/active-site region. For each independent replica, a center-of-mass steered molecular dynamics (SMD) simulation was used to generate a peptide-dissociation pathway. Configurations distributed along the resulting reaction coordinate were subsequently selected at approximately 0.1-nm intervals and subjected to equilibration followed by production umbrella sampling. The resulting biased trajectories were analyzed using the weighted histogram analysis method (WHAM) to reconstruct replica-specific potential of mean force (PMF) profiles. Because configuration selection was performed independently from each replica-specific SMD pathway, the exact configuration identities and numbers of successfully completed umbrella windows differ among the three calculations. The deposited datasets contain 60, 63, and 57 successfully completed umbrella windows for Replicas 1, 2, and 3, respectively. Only production windows included in the corresponding PMF reconstruction are retained in the archive. Each replica directory contains the SMD trajectory (pull.xtc) and corresponding GROMACS run-input file (pull.tpr), together with the production run-input files (umbrella_win*.tpr), restraint-force data (*_pullf.xvg), and reaction-coordinate data (*_pullx.xvg) for the successfully completed umbrella-sampling windows. Replica-specific PMF profiles, histogram-overlap data, and associated WHAM analysis outputs are provided within the corresponding Data_Analysis_PMF directories. The three independently reconstructed PMF profiles yielded PMF-derived binding-direction free-energy estimates of -17.61, -16.34, and -12.74 kcal mol⁻¹ for Replicas 1, 2, and 3, respectively, corresponding to a replica mean of -15.56 ± 2.53 kcal mol⁻¹. These values were calculated as the difference between the minimum and maximum of the corresponding zero-referenced one-dimensional PMF profiles and therefore describe the energetic separation between the sampled PMF states along the defined dissociation coordinate rather than an absolute standard-state binding free energy. Analysis of the averaged three-replica PMF yielded a maximum free-energy rise of 15.54 kcal mol⁻¹, with a bootstrap uncertainty of ±0.37 kcal mol⁻¹. SMP103 was represented using an explicitly bonded head-to-tail macrocyclic topology, and all enhanced-sampling calculations employed the CHARMM36 force field (charmm36-jul2021.ff) with the TIP3P water model. The small, human-readable molecular topology, SMD and umbrella-sampling parameter files, index groups, and replica-specific window-selection information are provided separately in the associated GitHub repository. The complete README included in this archive provides detailed descriptions of the deposited files and their organization. Associated enhanced-sampling input files:https://github.com/Olanrewaju-Durojaye/Enhanced-Sampling_Input_Files_for_the-_SMP103-Sortase_A_Complex Analysis scripts:https://github.com/Olanrewaju-Durojaye/Scripts_for_SMP_Project_analyses Associated replicated unbiased MD dataset:https://doi.org/10.5281/zenodo.21888186 Associated molecular dynamics input files:https://github.com/Olanrewaju-Durojaye/Molecular-Dynamics-Input-Files-for-De-Novo-Macrocyclic-Peptide-Sortase-A-Complexes