  Temperature Accelerated Sliced Sampling (TASS) is an efficient method to
compute high dimensional free energy landscapes. The original TASS method
employs the Weighted Histogram Analysis Method (WHAM) which is an iterative
post-processing to reweight and stitch high dimensional probability
distributions in sliced windows that are obtained in the presence of
restraining biases. The WHAM necessitates that TASS windows lie close to each
other for proper overlap of distributions and span the collective variable
space of interest. On the other hand, increase in number of TASS windows
implies more number of simulations, and thus it affects the efficiency of the
method. To overcome this problem, we propose herein a new mean-force (MF) based
reweighting scheme called TASS-MF, which enables accurate computation with a
fewer number of windows devoid of the WHAM post-processing. Application of the
technique is demonstrated for alanine di- and tripeptides in vacuo to compute
their two- and four-dimensional free energy landscapes, the latter of which is
formidable in conventional umbrella sampling and metadynamics. The landscapes
are computed within a kcal/mol accuracy, ensuring a safe usage for broad
applications in computational chemistry.
