Proteins with a long flexible polymeric tail attached at their N- or C-terminus are studied using molecular dynamics (MD) simulations of a coarse-grained model for protein folding where the temperature is regulated by either the Berendsen or the Langevin thermostat. These thermostats show different abilities to regulate the temperature of these systems that include flexible and more rigid regions. In the simulations with the Berendsen thermostat, the flexible tail is significantly hotter than the protein, both in its folded and unfolded states. Upon weakening the strength of the Berendsen thermostat, the temperature gradient between the fast and the slow degrees of freedom is significantly decreased, yet linkage between the temperatures of the flexible tail and the protein remains. The Langevin thermostat is proven to regulate the temperature of these inhomogenous systems reliably, without discriminating between the slow and fast degrees of freedom. The Langevin thermostat is less sensitive than is the Berendsen thermostat to the strength of the coupling between the protein system and the thermal bath. Our study calls for special care in choosing the thermostat for MD simulations of systems with inhomogenous degrees of freedom. Using the Berendsen thermostat with strong coupling would result in mistaken thermodynamic descriptions of such systems. (c) 2008 Wiley Periodicals, Inc.