Mean force based temperature accelerated sliced sampling: Efficient reconstruction of high dimensional free energy landscapes

Temperature accelerated sliced sampling (TASS) is an efficient method to compute high dimensional free energy landscapes. The original TASS employs the weighted histogram analysis (WHAM) which iterative post-processing reweight and stitch probability distributions in windows that are obtained presence of restraining biases. WHAM necessitates lie close each other for proper overlap span collective variable space interest. On hand, increase number implies more simulations, thus it affects efficiency method. To overcome this problem, we propose herein a new mean-force (MF) based reweighting scheme called TASS-MF, enables accurate computation with fewer devoid post-processing. Application technique demonstrated alanine di- tripeptides vacuo their two- four-dimensional landscapes, latter formidable conventional umbrella metadynamics. landscapes computed within kcal mol−1 accuracy, ensuring safe usage broad applications computational chemistry.