An implementation of hydrophobic force in implicit solvent molecular dynamics simulation for packed proteins.

MD simulations of five proteins in which helical chains are held together by hydrophobic packing were carried out to investigate the effect of hydrophobic force on simulated structures of these protein complexes in implicit generalized Born (GB) model. The simulation study employed three different methods to treat hydrophobic effect: the standard GB method that does not include explicit hydrophobic force, the LCPO method that includes explicit hydrophobic force based directly on solvent accessible surface area (SASA), and a proposed packing enforced GB (PEGB) method that includes explicit hydrophobic force based on the radius of gyration of the protein complex. Our simulation study showed that all five protein complexes were unpacked in the standard GB simulation (without explicit hydrophobic force). In the LCPO method, three of the five protein systems remained well packed during the simulation, indicating the need for an explicit hydrophobic force in GB model for these packed protein systems. However, two of the five systems were still unpacked during LCPO simulation. For comparison, all five protein systems remain well packed in simulation using the new PEGB method. Analysis shows that the failure of the LCPO method in two cases is related to the way that SASA changes during the unpacking process for these two systems. These examples showed that standard GB method without explicit hydrophobic force is not suitable for MD simulation of protein systems involving hydrophobic packing. A similar problem remains but to a much lesser extent in the LCPO method for some packed protein systems. The proposed PEGB method seems quite promising for MD simulation of large, multi-domain packed proteins in implicit solvent model.