Combined use of the weighted histogram analysis method (WHAM) and the free energy perturbation (FEP) method for the calculation of potential of mean force (PMF) from the molecular dynamics simulations is examined for the methane-methane association in TIP3P water with the SCAAS-model spherical boundary. The linear square fit of the informative free-energy profile from the WHAM, but with an uncertain baseline, to the discrete absolute free energies of binding from the FEP calculations yields the PMF with an accurate zero level. Such a procedure may be particularly useful in PMF simulations of biochemical systems when only a short part of the entire reaction pathways is considered. (c) 2007 Elsevier B.V. All rights reserved.