TY - JOUR
T1 - Computed Free Energies of Peptide Insertion into Bilayers are Independent of Computational Method
AU - Gumbart, James C.
AU - Ulmschneider, Martin B.
AU - Hazel, Anthony
AU - White, Stephen H.
AU - Ulmschneider, Jakob P.
PY - 2018/3/8
Y1 - 2018/3/8
N2 - We show that the free energy of inserting hydrophobic peptides into lipid bilayer membranes from surface-aligned to transmembrane inserted states can be reliably calculated using atomistic models. We use two entirely different computational methods: high temperature spontaneous peptide insertion calculations as well as umbrella sampling potential-of-mean-force (PMF) calculations, both yielding the same energetic profiles. The insertion free energies were calculated using two different protein and lipid force fields (OPLS protein/united-atom lipids and CHARMM36 protein/all-atom lipids) and found to be independent of the simulation parameters. In addition, the free energy of insertion is found to be independent of temperature for both force fields. However, we find major difference in the partitioning kinetics between OPLS and CHARMM36, likely due to the difference in roughness of the underlying free energy surfaces. Our results demonstrate not only a reliable method to calculate insertion free energies for peptides, but also represent a rare case where equilibrium simulations and PMF calculations can be directly compared.
AB - We show that the free energy of inserting hydrophobic peptides into lipid bilayer membranes from surface-aligned to transmembrane inserted states can be reliably calculated using atomistic models. We use two entirely different computational methods: high temperature spontaneous peptide insertion calculations as well as umbrella sampling potential-of-mean-force (PMF) calculations, both yielding the same energetic profiles. The insertion free energies were calculated using two different protein and lipid force fields (OPLS protein/united-atom lipids and CHARMM36 protein/all-atom lipids) and found to be independent of the simulation parameters. In addition, the free energy of insertion is found to be independent of temperature for both force fields. However, we find major difference in the partitioning kinetics between OPLS and CHARMM36, likely due to the difference in roughness of the underlying free energy surfaces. Our results demonstrate not only a reliable method to calculate insertion free energies for peptides, but also represent a rare case where equilibrium simulations and PMF calculations can be directly compared.
KW - Membrane
KW - Molecular dynamics
KW - Peptide partitioning
KW - Transfer free energy
KW - Translocon
UR - http://www.scopus.com/inward/record.url?scp=85043366034&partnerID=8YFLogxK
U2 - 10.1007/s00232-018-0026-y
DO - 10.1007/s00232-018-0026-y
M3 - Article
AN - SCOPUS:85043366034
SN - 0022-2631
SP - 1
EP - 12
JO - Journal of Membrane Biology
JF - Journal of Membrane Biology
ER -