The paper is organized as follows. First we present the underlying theory for the effect of mass changes and the stability of MD time integration. After describing the simulation and analysis methods, we construct a water model optimized for sampling efficiency. To validate our model, we show that TIP3P-F preserves the key thermodynamic and structural properties of TIP3P water. We proceed to demonstrate that for small peptides and RNA segments, which can be sampled extensively in standard MD, relevant structural and energetic properties are preserved. We then show that TIP3P-F enhances the sampling by comparing autocorrelation functions of widely studied observables. Finally, we show applications of TIP3P-F to full-length proteins, and lipid bilayers, again comparing the results to runs with regular TIP3P. Overall, we find that using TIP3P-F with a conventional time step of 2 fs speeds up conformational sampling of biomolecules up to about a factor of two over regular TIP3P at no additional cost in computation.