Mean Force Based Temperature Accelerated Sliced Sampling: Efficient Reconstruction of High Dimensional Free Energy Landscapes

TL;DR

This paper introduces TASS-MF, a mean-force based reweighting scheme that enhances temperature accelerated sliced sampling, allowing accurate high-dimensional free energy landscape reconstruction with fewer windows and no need for WHAM post-processing.

Contribution

The novel TASS-MF method improves efficiency by reducing the number of required windows and eliminating the need for WHAM, enabling accurate high-dimensional free energy calculations.

Findings

Accurately computed free energy landscapes within kcal/mol.

Demonstrated effectiveness on alanine di- and tripeptides.

Outperformed conventional umbrella sampling and metadynamics in high dimensions.

Abstract

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.