The Extended Generalized Adaptive Biasing Force Algorithm for Multidimensional Free-Energy Calculations

International audienceFree-energy calculations in multiple dimensions constitute a challenging problem, owing to the significant computational cost incurred to achieve ergodic sampling. The generalized adaptive biasing force (gABF) algorithm calculates n one-dimensional lists of biasing forces to approximate the n-dimensional matrix by ignoring the coupling terms ordinarily taken into account in classical ABF simulations, thereby greatly accelerating sampling in the multidimensional space. This approximation may however occasionally lead to poor, incomplete exploration of the conformational space compared to classical ABF, especially when the selected coarse variables are strongly coupled. It has been found that introducing extended potentials coupled to the coarse variables of interest can virtually eliminate this shortcoming, and, thus, improve the efficiency of gABF simulations. In the present contribution, we propose a new free-energy method, coined extended generalized ABF (egABF), combining gABF with an extended Lagrangian strategy. The results for three illustrative examples indicate that (i) egABF can explore the transition coordinate much more efficiently compared with classical ABF, eABF, and gABF, in both simple and complex cases and (ii) egABF can achieve a higher accuracy than gABF, with a root mean-squared deviation between egABF and eABF free-energy profiles on the order of kBT. Furthermore, the new egABF algorithm outruns the previous ABF-based algorithms in high-dimensional free-energy calculations and, hence, represents a powerful importance-sampling alternative for the investigation of complex chemical and biological processes