Abundant peptides and proteins containing @entity369 ( @entity534 ) and @entity376 ( @entity9108 ) @entity3534 can apparently permeate cell membranes with ease. However, the mechanisms by which these peptides and proteins succeed in traversing the free energy barrier imposed by cell membranes remain largely unestablished. Precise thermodynamic studies (both theoretical and experimental) on the interactions of @entity534 and @entity9108 residues with model lipid bilayers can provide valuable clues to the efficacy of these cationic peptides and proteins. We have carried out molecular dynamics simulations to calculate the interactions of ionized @entity534 and @entity9108 side-chains with the zwitterionic @entity26291 ( @entity4748 ) lipid bilayer for 10 widely used lipid/protein force fields: CHARMM36/CHARMM36, SLIPID/AMBER99SB-ILDN, OPLS-AA/OPLS-AA, Berger/OPLS-AA, Berger/GROMOS87, Berger/GROMOS53A6, GROMOS53A6/GROMOS53A6, nonpolarizable MARTINI, polarizable MARTINI, and BMW MARTINI. We performed umbrella sampling simulations to obtain the potential of mean force for @entity534 and @entity9108 side-chains partitioning from water to the bilayer interior. We found significant differences between the force fields, both for the interactions between side-chains and bilayer surface, as well as the free energy cost for placing the side-chain at the center of the bilayer. These simulation results were compared with the Wimley-White interfacial scale. We also calculated the free energy cost for transferring ionized @entity534 and @entity9108 side-chains from water to both dry and wet @entity10333 . Our simulations reveal rapid diffusion of water molecules into @entity10333 whereby the equilibrium mole fraction of water in the wet @entity10333 phase was    25%. Surprisingly, our free energy calculations found that the high water content in wet @entity10333 lowered the water-to- @entity10333 partitioning free energies for cationic residues by only 0.6 to 0.7 kcal/mol.

Evaluating Force Fields for the Computational Prediction of Ionized XXXX and @entity376 Side-Chains Partitioning into Lipid Bilayers and @entity10333 .

@entity3534 :: ('MESH:D000596', 'Chemical') :: ['amino acids'] @entity534 :: ('CHEBI:16467', 'Chemical') :: ['Arg'] @entity9108 :: ('CHEBI:29967', 'Chemical') :: ['Lys'] @entity4748 :: ('CHEBI:40265', 'Chemical') :: ['DPPC'] @entity10333 :: ('CHEBI:37868', 'Chemical') :: ['octanol'] @entity376 :: ('CHEBI:25094', 'Chemical') :: ['lysine'] @entity26291 :: ('MESH:C081581', 'Chemical') :: ['1,2-dipalmitoyl-sn-glycero-3-phosphocholine'] @entity369 :: ('CHEBI:29016', 'Chemical') :: ['arginine']
@entity369 :: (CHEBI:29016,Chemical) :: ['Arginine']
