A generalized Langevin dynamics approach to model solvent dynamics effectson proteins via a solvent-accessible surface. The carboxypeptidase A inhibitor protein as a model
B. Oliva et al., A generalized Langevin dynamics approach to model solvent dynamics effectson proteins via a solvent-accessible surface. The carboxypeptidase A inhibitor protein as a model, THEOR CH AC, 105(2), 2000, pp. 101-109
A generalized Langevin dynamics (GLD) scheme is derived for (bio)macromolec
ules having internal structure, arbitrary shapes and a size larger than sol
vent molecules (i.e. proteins). The concept of solvent-accessible surface a
rea (SASA) is used to incorporate solvent effects via external forces there
by avoiding its explicit molecular representation. A simulation algorithm i
s implemented in the GROMOS molecular dynamics (MD) program including rando
m forces and memory effects, while solvation effects enter via derivatives
of the surface area. The potato carboxypeptidase inhibitor (PCI), a small p
rotein, is used to numerically test the approach. This molecule has N- and
C-terminal tails whose structure and fluctuations are solvent dependent. A
1-ns MD trajectory was analyzed in depth. X-ray and NMR structures are used
in conjunction with MD simulations with and without explicit solvent to ga
uge the quality of the results. All the analyses showed that the GLD simula
tion approached the results obtained for the MD simulation with explicit si
mple-point-charge-model water molecules. The SASAs of the polar atoms show
a natural exposure towards the solvent direction. A FLS solvent simulation
was completed in order to sense memory effects. The approach and results pr
esented here could be of great value for developing alternatives to the use
of explicit solvent molecules in the MD simulation of proteins, expanding
its use and the time-scale explored.