adaptive biasing force
Overcoming free energy barriers in molecular simulations using an average force

Historical background

Theoretical foundations
Success stories
Contact us

Historical background

Original method

Combines three novel ideas:
  • unconstrained thermodynamic integration
  • adaptive bias based on a local, running estimate of the free energy derivative
  • a new expression for the free energy derivative

Andrew Pohorille

NASA Ames Research Center, Moffett Field, California, and
University of California, San Francisco, USA

Eric Darve

Stanford University, Palo Alto, California, USA


  1. Darve, E.; Pohorille, A. Calculating free energies using average force, J. Chem. Phys. 2001, 115, 9169–9183.
  2. Darve, E.; Wilson, M. A.; Pohorille, A. Calculating free energies using a scaled-force molecular dynamics algorithm, Mol. Sim. 2002, 28, 113-144.
  3. Rodriguez-Gomez, D.; Darve, E.; Pohorille, A. Assessing the efficiency of free energy calculation methods. J. Chem. Phys. 2004, 120, 3563-3578.
  4. Darve, E.; Rodriguez-Gomez, D.; Pohorille, A. Adaptive biasing force method for scalar and vector free energy calculations, J. Chem. Phys. 2008, 128, 144120.

NAMD implementation

Brings together the efficiency of ABF sampling and the scalability of NAMD for large biomolecular simulations. Starting with NAMD 2.7, ABF is integrated in the Collective Variables module, a flexible framework for biased MD simulations.

Jérôme Hénin

LISM, CNRS and Aix-Marseille Université, Marseille, France

Chris Chipot

Nancy Université, Vandoeuvre-lès-Nancy, France


  1. Hénin, J.; Chipot, C. Overcoming free energy barriers using unconstrained molecular dynamics simulations. J. Chem. Phys. 2004, 121, 2904-2914.
  2. Chipot, C.; Hénin, J. Exploring the free-energy landscape of a short peptide using an average force. J. Chem. Phys. 2005, 123, 244906.
  3. Hénin, J.; Fiorin, J.; Chipot, C.; Klein, M.L. Exploring Multidimensional Free Energy Landscapes Using Time-Dependent Biases on Collective Variables. J. Chem. Theory Comput. 2010, 6, 35-47


Webpage by Jérôme Hénin and Chris Chipot, ©2010.