A multiple time step algorithm compatible with a large number of distance classes and an arbitrary distance dependence of the time step size for the fast evaluation of nonbonded interactions in molecular simulations

A new algorithm is introduced to perform the multiple time step integration of the equations of motion for a molecular system, based on the splitting of the nonbonded interactions into a series of distance classes. The interactions between particle pairs in successive classes are updated at a progressively decreasing frequency. Unlike previous multiple time‐stepping schemes relying on distance classes, the present algorithm sorts interacting particle pairs by their next update times rather than by their update frequencies. For this reason, the proposed scheme is extremely flexible with respect to the number of classes that can be employed (up to hundred or more) and the distance dependence of the relative time step size (arbitrary integer function of the distance). It can also easily be adapted to classes defined based on a criterion other than the interparticle distance (e.g., interaction magnitude). Different variants of the algorithm are tested in terms of accuracy and efficiency for simulations of a pure water system (6167 molecules) under truncated‐octahedral periodic boundary conditions, and compared to the twin‐range method standardly used with GROMOS96 (short‐ and long‐range cutoff distances of 0.8 and 1.4 nm, pair list and intermediate‐range interactions updated every five steps). In particular, multiple time‐stepping schemes with an accuracy comparable to that of the twin‐range method can be designed, that permit to increase the effective (long‐range) cutoff distance from 1.4 to 3.0 nm with a performance loss of only about a factor 2. This result is quite encouraging, considering the benefits of doubling the cutoff radius in the context of (bio‐)molecular simulations. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1163–1176, 2006