Conformational and energetic effects of truncating nonbonded interactions in an aqueous protein dynamics simulation

In a previous aqueous protein dynamics study, we compared the rms deviation relative to the crystal structure for distance‐dependent and constant dielectric models with and without a nonbonded cutoff. The structures obtained from a constant dielectric simulation with a cutoff were substantially different from the structures obtained from a distance‐dependent dielectric simulation, with and without cutoff, and a constant dielectric model without a cutoff. In fact, structures from the distance‐dependent dielectric simulations were insensitive to the nonbonded cutoff and in good agreement with the structures generated from the constant dielectric simulation without a cutoff. In addition, the solute‐solvent temperature differential and solvent evaporation artifacts, characteristic of the constant dielectric simulation with a cutoff, were not present for the distance‐dependent dielectric simulations. In this current work, we explore whether this dielectric‐dependent cutoff‐sensitive behavior for a constant dielectric model arises from the discontinuities in the forces at the nonbonded cutoff or from neglecting the structure‐stabilizing interactions beyond the nonbonded cutoff. We also examine the origin of the dielectric‐dependent artifacts, and its potential influence on the structural disparity. Several protocols for protein dynamics simulations are compared using both constant and distance‐dependent dielectric models, including implementation of a switching function and a nonbonded cutoff and two different temperature coupling algorithms. We show that the distance‐dependent dielectric model conserves energy in the SPASMS molecular mechanics and dynamics software for the time steps and nonbonded cutoffs commonly used in macromolecule simulations. Although the switching function simulation also conserved energy over a range of commonly used cutoffs, the constant dielectric model with a switching function yielded conformational results more similar to a constant dielectric simulation without a switching function than to a constant dielectric model without a nonbonded cutoff. Therefore, the conformational disparity between the dielectric models arises from neglecting important structure‐stabilizing interactions beyond the cutoff, rather than differences in energy conservation. © 1993 John Wiley & Sons, Inc.