Table 1 Symmetric and asymmetric depth-dependent potentials derived from experimental data or statistics.
From: Statistically derived asymmetric membrane potentials from α-helical and β-barrel membrane proteins
author | year | α/β a | E/S b | S/A c | ref | comments | #prot d | embedding e | SASA f | bin size | functional form |
|---|---|---|---|---|---|---|---|---|---|---|---|
Hessa & von Heijne, biological scale | 2007 | α | exp | sym | Inserted a TM segment into the leader peptidase protein, into which all amino acids were introduced at different depths. Translocation into microsomes was quantified by the number of glycosylation sites on either terminus of the TM segment. 324 19-residue TM segments were measured to compute ΔΔG’s | 1 | center of TM segment is at membrane center | protein is 3-helix bundle, so most are lipid-exposed | residue | double Gaussian for WY, single Gaussian for others | |
Elazar & Fleishman, dsTbL | 2016 | α | exp | asym | Combined sequence libraries with TOXCAT assay in whole cells. Measured TM span expression, insertion and association depending on residue depth with orthogonal antibiotic resistance markers. 472 mutants were tested 100 times each in a high-throughput manner to compute ΔΔG’s | 1 | membrane center was estimated by aligning ILMF profiles’ troughs | single helix, so all lipid-exposed | residue | 4 D polynomials | |
Senes & DeGrado, Ez potential | 2007 | α | stat | sym | statistical potential derived from 24 MPs in a symmetric manner; insufficient counts for C | 24 | protein COM at membrane center | no distinction | 2 Å | double Gaussian for WY, sym sigmoidal for others | |
Ulmschneider, implicit membrane potential | 2005 | α | stat | asym | statistical potential derived from 46 MPs in an asymmetric manner; resolution ≤4 Å; insufficient counts for CST; | 46 | centered DSSP TM spans at membrane center | SASA probe radius 1.4 Å | 2 Å | double Gaussian for RKDEHWY, single Gaussian else | |
Schramm & DeGrado, Ez potential | 2012 | α | stat | asym | statistical potential derived from 76 MPs in an asymmetric manner; sequence similarity ≤30%, resolution ≤ 3.5 Å | 76 | OPM embedding | SASA probe radius 1.9 Å | 2 Å | sigmoid, Gaussian or combination of the two | |
this work | 2018 | α | stat | asym | this | statistical potential derived from 239 MPs in an asymmetric manner; sequence similarity ≤30%, resolution ≤3 Å | 239 | topology from OPM but embedding from PDBTM | lipid-exposed vs buried35 | 3 Å | double Gaussian |
Moon & Fleming, sidechain hydrophobicity scale | 2011 | β | exp | sym | reversible GnHCl (un)folding of OmpLA into DLPC vesicles to derive symmetric profile; an A residue at the membrane center was mutated into all 19 other amino acids; 3 titrations for WT and 2 titrations for mutants to compute ΔΔG’s; potential derived for LR | 1 | membrane center set halfway between aromatic girdles | only lipid-exposed residues | residue | single Gaussian for LR, no fit parameters given | |
MacDonald & Fleming, sidechain hydrophobicity scale | 2016 | β | exp | sym | reversible GnHCl (un)folding of OmpLA into DLPC vesicles; residues at different depths were mutated into WYF; 3 titrations for WT and 2 titrations for mutants to compute ΔΔG’s; | 1 | center from MD simulations: COM of the protein and phosphate atoms | only lipid-exposed residues | residue | linear for WYF | |
Hsieh & Nanda, Ez potential | 2012 | β | stat | sym | statistical potential derived from 35 MPs in a symmetric manner; sequence similarity ≤26%; insufficient counts for CM | 35 | embedding from OPM TM spans | SASA > 0.2 | 3 Å | double Gaussian for WYFG, sym sigmoid for others | |
Wimley | 2002 | β | stat | asym | statistical 3-state hydrophobicity scale from 15 non-redundant β-barrels; | 15 | aromatic girdles were used | lipid vs water exposed | regions | no fitting done | |
Jackups & Liang, positive outside rule | 2006 | β | stat | asym | sequence similarity ≤ 26%; resolution ≤2.6 Å; derived statistics for regions, depending on z and burial, but no depth-dependent potential like the others, they use it to derive a basic energy function for barrel prediction based on H-bonds | 19 | embedding from OPM TM spans | regions | regions | no fitting done | |
Slusky & Dunbrack, charge outside rule | 2013 | β | stat | asym | statistical potential derived from 55 MPs in an asymmetric manner; sequence similarity ≤50%; resolution ≤3.5 Å; only averages of AA groups were fit, but not individual AA types; insufficient counts for PCMT | 55 | N/C termini are inside, membrane center defined where phospholipid meets LPS and aromatic girdle set to −12Å | lipid vs water exposed | 3 Å | RKDE to P2, NQHS to P2, AGILV to P2, FWY to P4, no fitting parameters given | |
Lin & Liang, TMSIP | 2017 | β | stat | asym | 19 MPs were used to derive an energy function that includes a membrane burial term and inter- and intra-strand H-bond interaction energies27, the energy function was used to derive a statistical potential for ΔΔG’s tested on 24 MPs; sequence similarity ≤26%; resolution ≤2.6 Å | 19 | embedding from OPM TM spans | lipid vs water exposed | residue (regions for deri- vation) | double Gaussian for WY, single Gaussian for others | |
this work | 2018 | β | stat | asym | this | statistical potential derived from 96 MPs in an asymmetric manner; sequence similarity ≤50%, resolution ≤3 Å; insufficient counts for C | 96 | topology from OPM but embedding from PDBTM | lipid-exposed vs buried35 | 3 Å | 4D polynomial for IM, double Gaussian for others |
