Low-mass molecular dynamics simulation for configurational sampling enhancement: More evidence and theoretical explanation

It has been reported recently that classical, isothermal-isobaric molecular dynamics (NTP MD) simulations at a time step of 1.00 fs of the standard-mass time (Δt=1.00 fssmt) and a temperature of ≤340 K using uniformly reduced atomic masses by tenfold offers better configurational sampling than standard-mass NTP MD simulations at the same time step. However, it has long been reported that atomic masses can also be increased to improve configurational sampling because higher atomic masses permit the use of a longer time step. It is worth investigating whether standard-mass NTP MD simulations at Δt=2.00 or 3.16 fssmt can offer better or comparable configurational sampling than low-mass NTP MD simulations at Δt=1.00 fssmt. This article reports folding simulations of two β-hairpins showing that the configurational sampling efficiency of NTP MD simulations using atomic masses uniformly reduced by tenfold at Δt=1.00 fssmt is statistically equivalent to and better than those using standard masses at Δt=3.16 and 2.00 fssmt, respectively. The results confirm that, relative to those using standard masses at routine Δt=2.00 fssmt, the low-mass NTP MD simulations at Δt=1.00 fssmt are a simple and generic technique to enhance configurational sampling at temperatures of ≤340 K.