PLUMED is a portable plugin designed for free-energy calculations in molecular systems, particularly focusing on biological problems. It interfaces with popular classical molecular dynamics (MD) codes such as GROMACS, NAMD, DL-POLY, and SANDER, allowing users to perform enhanced sampling techniques like metadynamics, umbrella sampling, and Jarzynski equation-based methods. The software is written in ANSI-C and can be easily integrated with Fortran and C/C++ codes. PLUMED supports various collective variables (CVs) and provides tools for analyzing the results, such as the COLVAR file for storing CV values and the HILLS file for metadynamics simulations. The plugin is available for download and can be used with different MD codes, offering flexibility in choosing the appropriate code based on specific application requirements.PLUMED is a portable plugin designed for free-energy calculations in molecular systems, particularly focusing on biological problems. It interfaces with popular classical molecular dynamics (MD) codes such as GROMACS, NAMD, DL-POLY, and SANDER, allowing users to perform enhanced sampling techniques like metadynamics, umbrella sampling, and Jarzynski equation-based methods. The software is written in ANSI-C and can be easily integrated with Fortran and C/C++ codes. PLUMED supports various collective variables (CVs) and provides tools for analyzing the results, such as the COLVAR file for storing CV values and the HILLS file for metadynamics simulations. The plugin is available for download and can be used with different MD codes, offering flexibility in choosing the appropriate code based on specific application requirements.