Supporting information for the paper Mechanisms of Tecovirimat Antiviral Activity and Poxvirus Resistance

ABFE section

Monomer and dimmer simulations

archive.tar.gz

• - BindFLow-inputs: All the necesarry files to run BindFlow and obtain the reported results. Consider that 2 MD simulaitons are almost never the same.
• - fep-openff-2.0.0_light and fep-openff-2.0.0-monomer_light: Presents a minimalist set of files to reproduce the calculations for the dimmer and monomer respectivelly:
  • Molecular Dynamic Parameters (MDP file) of each stage
  • Topology files (TOP file)
  • dh/dlambda for all perturbation (XVG file)
  • Configuration files of key steps (GRO file)
• For each COMPLEX there is one directory ligand. Inisde of it you will find an input directory which have the TOP, GRO, NDX and ITP files necesary to perform the MD simulation. In the case of the complex simulations, you will find in all the replicas directories in complex/equil-mdsim/boreschcalc the GRO and TOP files that were used as input for the FEP complex simulaitons. Specifically in complex/fep/topology the topology of the complex after adding the boresch restraint information. The last topology is the real input for all FEP calculations in the complex.

ABFE validation

archive-ABFE-validation.tar.gz

These simulations were conducted to validate our Absolute Binding Free Energy (ABFE) pipeline on this system. The directory mirrors the structure of archive.tar.gz and includes seven structurally similar tecovirimat ligands, as well as tecovirimat itself. References for the experimental data can be found at:

[Primary reference] Bailey, T. R., Rippin, S. R., Opsitnick, E., Burns, C. J., Pevear, D. C., Collett, M. S., ... & Jordan, R. (2007). N-(3, 3a, 4, 4a, 5, 5a, 6, 6a-Octahydro-1, 3-dioxo-4, 6-ethenocycloprop [f] isoindol-2-(1 H)-yl) carboxamides: Identification of Novel Orthopoxvirus Egress Inhibitors. Journal of medicinal chemistry, 50(7), 1442-1444.

Tables of final calculations (fep_results*)

Sumary tables of the calculations.