High-Dimensional Enhanced Sampling via Regularized Path-Dependent McKean--Vlasov Dynamics using Tensor Density Approximation
This work addresses the scalability bottleneck of enhanced sampling methods for high-dimensional collective variables, which is a key problem in computational chemistry and molecular dynamics.
The paper proposes a regularized path-dependent McKean-Vlasov formulation for enhanced sampling in high-dimensional collective variable spaces, replacing variational regularization with direct density regularization and using a weighted path-history measure for stability. Numerical experiments show effectiveness for CV dimensions up to 64.
Sampling from high-dimensional Gibbs measures poses a challenge when the energy landscape consists of multiple metastable states. Enhanced-sampling methods mitigate this difficulty by introducing adaptive biasing potentials to facilitate the exploration along prescribed collective variables (CVs), but their scalability is often limited by the dimension of the CV space. Motivated by the Wasserstein-gradient-flow interpretation of adaptive biasing, we propose a regularized path-dependent McKean--Vlasov formulation for high-dimensional enhanced sampling. The formulation replaces the variational regularization of the Wasserstein functional by a direct regularization of the CV marginal density in the McKean--Vlasov drift, avoiding the outer convolution over the CV domain. Furthermore, it replaces the instantaneous law by a weighted path-history measure to improve statistical stability in the small-replica regime. We establish well-posedness of the resulting regularized and path-dependent stochastic dynamics under suitable assumptions. For numerical realization, the history-averaged CV marginal density is approximated using an optimization-free functional hierarchical tensor representation, leading to a scalable density-based adaptive biasing scheme. Numerical experiments on benchmark potentials and molecular systems demonstrate the effectiveness of the proposed method for sampling problems with CV dimensions up to 64.