Potential of mean force calculations of ligand binding to ion channels from Jarzynski's equality and umbrella sampling.
Potential of mean force (PMF) calculations provide a reliable method for determination of the absolute binding free energies for protein-ligand systems. The common method used for this purpose -- umbrella sampling with weighted histogram analysis -- is computationally very laborious, which limits its applications. Recently, a much simpler alternative for PMF calculations has become available, namely, using Jarzynski's equality in steered molecular dynamics simulations. So far, there have been a few comparisons of the two methods and mostly in simple systems that do not reflect the complexities of protein-ligand systems. Here, we use both methods to calculate the PMF for ion permeation and ligand binding to ion channels. Comparison of results indicate that Jarzynski's method suffers from relaxation problems in complex systems and would require much longer simulation times to yield reliable PMFs for protein-ligand systems.
Baştuğ
Turgut
T
Faculty of Arts and Sciences, TOBB University of Economics and Technology, Ankara, Turkey.
Chen
Po-Chia
PC
Patra
Swarna M
SM
Kuyucak
Serdar
S
D001665:Binding Sites; D003198:Computer Simulation; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry* / Q000648:ultrastructure*; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D011188:Potassium / Q000737:chemistry*; D011485:Protein Binding; D013314:Stress, Mechanical
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D008024:Ligands; D011188:Potassium