Molecular Dynamics Simulations using Temperature Enhanced Essential dynamics Replica EXchange (TEE-REX)

Todays standard molecular dynamics (MD) simulations of moderately sized biomolecular systems at full atomic resolution are typically limited to the nanosecond timescale and therefore suffer from limited conformational sampling. Efficient ensemble-preserving algorithms like replica exchange (REX) may alleviate this problem somewhat but are still computationally prohibitive due to the large number of degrees of freedom involved. Aiming at increased sampling efficiency we present a novel simulation method combining the ideas of essential dynamics and replica exchange. Unlike standard REX, in each replica only a selection of essential collective modes of a subsystem of interest (essential subspace) are coupled to a higher temperature with the remainder of the system staying at a reference temperature T0. This selective excitation along with the replica framework permits efficient approximate ensemble-preserving conformational sampling and allows much larger temperature differences between replicas, thereby considerably enhancing sampling efficiency. Ensemble properties and sampling performance of the method are discussed using dialanine and guanylin test systems with multi-microsecond MD simulations of these test systems serving as references.