Self-avoiding
conformational sampling (SACS) is proposed as an
enhanced conformational sampling method for proteins. In SACS, the
following conformational resampling is repeated for a given protein:
(1) identification of newly visited states in a subspace and (2) conformational
resampling by restarting short-time molecular dynamics (MD) simulations
from the newly visited states. To identify the newly visited states,
a set of history-dependent histograms projected onto the subspace
is used. One is constructed from the trajectories sampled at the current
(<i>i</i>th) cycle, and the other is constructed from all
of the trajectories accumulated up through the previous ((<i>i</i> – 1)th) cycle. By reference to the history-dependent
histograms, the newly visited states appearing at the current (<i>i</i>th) cycle are defined as a difference set between them.
By repeating the cycle of conformational resampling, SACS prevents
the system from revisiting states that have already been visited for
previous cycles, promoting structural transitions via resampling from
the newly visited states. To verify the conformational sampling efficiency
of SACS, the present method was applied to reveal underlying mechanisms
of biologically important domain motions of maltodextrin binding protein
in explicit water and successfully reproduced the open–closed
transition with a reasonable (nanosecond-order) computational cost
