A sampling and docking program.

The S4MPLE program is by design providing an unified approach to all subclasses of conformational sampling problems : it is competent for conformational sampling (including small protein folding), rigid docking, flexible docking (including whole flexible protein loops, not only side chains), multi-ligand docking (simultaneous docking of several fragment-like binders, or docking with mobile waters), covalent docking (docking of a ligand moiety only, while the other half is already placed in the site and fixed – useful in ligand growths/fragment linking in fragment-based drug design), molecular self-assembly (the “site” needs not be a protein – no requirements to have a site made of aminoacid residues).

Screenshots of results

Flexible Fragment-to-Lead Growth, with side chain rearrangements

Docking, with locally flexible backbone and mobile crystallographic water molecules


Linux64 command line


Documentation is available here


L. Hoffer, D. Horvath


Hoffer, L., & Horvath, D.
S4MPLE—sampler for multiple protein-ligand entities : simultaneous docking of several entities.
J Chem Inf Model. 2013 Jan 28 ;53(1):88-102. doi : 10.1021/ci300495r

Hoffer, L., Chira, C., Marcou, G., Varnek, A., & Horvath, D.
S4MPLE—Sampler for Multiple Protein-Ligand Entities : Methodology and Rigid-Site Docking Benchmarking.
Molecules. 2015 May 19 ;20(5):8997-9028. doi : 10.3390/molecules20058997.

Hoffer, L. ; Renaud, J.-P. ; Horvath, D.,
In Silico Fragment-Based Drug Discovery : Setup and Validation of a Fragment-to-Lead Computational Protocol Using S4MPLE.
J. Chem. Inf. Model. 53 (4), 836-51 (2013)


The single-CPU distribution of this software is freely available. The package includes the sampling and docking program S4MPLE, including User guide, Force field data, scripts and tools for ligand preparation, supplementary benchmarking data.

Please please fill the form available here to request a download link for this version.

However, since S4MPLE is under steady development, it is advised to contact Dragos Horvath ( for the latest versions.