Markov state models (MSMs) have proven valuable in studying the dynamics of protein conformational changes via statistical analysis of molecular dynamics simulations. In MSMs, the complex configuration space is coarse-grained into conformational states, with dynamics modeled by a series of Markovian transitions among these states at discrete lag times. Constructing the Markovian model at a specific lag time necessitates defining states that circumvent significant internal energy barriers, enabling internal dynamics relaxation within the lag time. This process effectively coarse-grains time and space, integrating out rapid motions within metastable states. Thus, MSMs possess a multiresolution nature, where the granularity of states can be adjusted according to the time-resolution, offering flexibility in capturing system dynamics. This work introduces a continuous embedding approach for molecular conformations using the state predictive information bottleneck (SPIB), a framework that unifies dimensionality reduction and state space partitioning via a continuous, machine learned basis set. Without explicit optimization of the VAMP-based scores, SPIB demonstrates state-of-the-art performance in identifying slow dynamical processes and constructing predictive multiresolution Markovian models. Through applications to well-validated mini-proteins, SPIB showcases unique advantages compared to competing methods. It autonomously and self-consistently adjusts the number of metastable states based on a specified minimal time resolution, eliminating the need for manual tuning. While maintaining efficacy in dynamical properties, SPIB excels in accurately distinguishing metastable states and capturing numerous well-populated macrostates. This contrasts with existing VAMP-based methods, which often emphasize slow dynamics at the expense of incorporating numerous sparsely populated states. Furthermore, SPIB's ability to learn a low-dimensional continuous embedding of the underlying MSMs enhances the interpretation of dynamic pathways. With these benefits, we propose SPIB as an easy-to-implement methodology for end-to-end MSM construction.
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