A generalized Langevin dynamics approach to model solvent dynamics effectson proteins via a solvent-accessible surface. The carboxypeptidase A inhibitor protein as a model

Citation
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
Citations number
44
Categorie Soggetti
Physical Chemistry/Chemical Physics
Journal title
THEORETICAL CHEMISTRY ACCOUNTS
ISSN journal
1432881X → ACNP
Volume
105
Issue
2
Year of publication
2000
Pages
101 - 109
Database
ISI
SICI code
1432-881X(200012)105:2<101:AGLDAT>2.0.ZU;2-E
Abstract
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.