Integrating All-Atom and Coarse-Grained SimulationsToward Understanding of IDPs at Surfaces

We present a scheme
for transferring conformational degrees of
freedom from all-atom (AA) simulations of an intrinsically disordered
protein (IDP) to coarse-grained (CG) Monte Carlo (MC) simulations
using conformational swap moves. AA simulations of a single histatin
5 peptide in water were used to obtain a structural ensemble, which
is reweighted in a CGMC simulation in the presence of a negatively
charged surface. For efficient sampling, the AA trajectory was condensed
using two approaches: RMSD clustering (based on the root-mean-square
difference in atom positions) and a “naı̈ve”
truncation, where only every 100th frame of the trajectory was included
in the library. The results show that even libraries with few structures
well reproduce the radius of gyration and interaction free energy
as functions of the distance from the surface. We further observe
that the surface slightly promotes the secondary structure of histatin
5 and more so if using explicit surface charges rather than smeared
charges.