The free energy landscape of small peptides as obtained from metadynamics with umbrella sampling corrections.
There is considerable interest in developing methodologies for the accurate evaluation of free energies, especially in the context of biomolecular simulations. Here, we report on a reexamination of the recently developed metadynamics method, which is explicitly designed to probe "rare events" and areas of phase space that are typically difficult to access with a molecular dynamics simulation. Specifically, we show that the accuracy of the free energy landscape calculated with the metadynamics method may be considerably improved when combined with umbrella sampling techniques. As test cases, we have studied the folding free energy landscape of two prototypical peptides: Ace-(Gly)(2)-Pro-(Gly)(3)-Nme in vacuo and trialanine solvated by both implicit and explicit water. The method has been implemented in the classical biomolecular code AMBER and is to be distributed in the next scheduled release of the code.
Babin
Volodymyr
V
Center for High Performance Simulations (CHiPS), North Carolina State University, Raleigh, NC 27695, USA.
Roland
Christopher
C
Darden
Thomas A
TA
Sagui
Celeste
C
D000465:Algorithms; D003198:Computer Simulation; D004735:Energy Transfer; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation
D010455:Peptides