We report the results of a molecular dynamics (MD) study of the effects of confinement and molecular crowding on the thermodynamics and kinetics of folding of a 46 residue off-lattice minimalist beta-barrel protein. Crowding was mimicked by restricting the protein to a sphere with a soft well repulsive potential. MD simulations were performed on the protein in an unconfined environment, as well as confined to spheres of two different radii, 5.88sigma and 11.76sigma. Here, sigma is the bond length between two adjacent residues and the radius of gyration of the protein in its native state is 2.87sigma. We find that for the larger sphere (11.76sigma), the folding and collapse temperatures are virtually unchanged from their bulk values, but the average folding time is decreased by 35%. By contrast, the smaller sphere has a much more significant thermodynamic effect (the folding temperature is raised by 28%) but the average folding time is only decreased by 58%. Confinement is also seen to restrict the conformational space accessible to the protein in its denatured state. In addition, confinement appears to change the folding mechanism for this protein, as long-lived intermediates present in the bulk are both modified and have shorter lifetimes when the protein is confined. (C) 2003 American Institute of Physics.