LAMBADA & InflateGRO2: Efficient Membrane Alignment and Insertion ...
SUPPORTING INFORMATION
LAMBADA & InflateGRO2: Efficient Membrane Alignment and Insertion of Membrane Proteins for Molecular Dynamics Simulations
Thomas H. Schmidt, Christian Kandt* Computational Structural Biology, Department of Life Science Informatics B-IT, Life & Medical Sciences (LIMES) Center, University of Bonn, Dahlmannstr. 2, 53113 Bonn, Germany
Corresponding Author * Email: [email protected], Phone: #49 228 2699 324; Fax: #49 228 2699 341
Supplemental table 1: Additional set of LAMBADA test proteins Protein (PDB-ID)
Residues
TM Structure
Internal TM Cavity
Alignment time* + Orientation
Orientation deviation (compared to OPM)
Proton channel M2 (2RLF)1
152
Conical
Yes
6s
45 s
21.440°
Bovine rhodopsin (1GZM)2
328
Cylindrical
No
6s
2’ 27 s
12.945°
436
Cylindrical
Yes
6s
1’ 37 s
3.041°
684
Cylindrical
Yes
7s
3’ 23 s
0.014°
824
Irregular
No
8s
2’ 34 s
10.568°
P-glycoprotein (3G5U)6
1182
Conical
No
10 s
4’ 25 s
6.157°
Vitamin B12 transporter BtuCDF (2QI9)7
1389
Irregular
No
10 s
4’ 16 s
6.472°
CorA Mg2+ transporter (2BBJ)8
1670
Irregular
No
12 s
6’ 14 s
0.813°
Maltose (2R6G)9
1887
Irregular
No
12 s
6’ 21 s
6.284°
6729
Irregular
No
34 s
23’ 56 s
2.941°
5-lipoxygenase-activating (FLAP) (2Q7M)3
protein
Bacteriorhodopsin (1QHJ)4 Photosynthetic (3V3Y)5
reaction
transporter
Photosystem I (1JB0)10
center
MalGFK-E
*performed using a single core on a 4 GB RAM DELL Precision 390 workstation (CPU: Intel® Core™2 6700 2x2.66 GHz)
Supplemental figure 1: LAMBADA output for an additional set of ten membrane proteins of different size and transmembrane structure. For each protein the membrane-embedded LAMBADA prediction is compared to the corresponding entry in the orientation of proteins in membranes (OPM) database. Lipid head groups are colored in blue, charged proteins residues are red, hydrophobic residues appear white. For the LAMBADA results the protein’s hydrophobic belt region is highlighted in yellow. LAMBADA correctly aligns each test protein yielding either equivalent (1GZM, 2Q7M, 1QHJ, 3V3Y, 3G5U, 2QI9, 2BBJ, 2R6G, 1JB0) or better results (2RLF) compared to the OPM data base.
Supplemental figure 2: In three cases of the first set of nine test proteins the LAMBADA orientations differed between 9° and 10° from the predictions made by the orientation of protein in membrane (OPM) database. Comparing the OPM (left) and LAMBADA orientations (right) side by side, we find that for the outer membrane protein OmpX (PDB-ID: 1QJ9) (a) and the outer membrane phospholipase A (PDB-ID: 1QD5) (b), the LAMBADA prediction yields a better match between hydrophobic belt and lipid bilayer, whereas for the lipid A deacylase LpxR (PDB-ID: 3FID) (c) both orientations appear equally valid.
REFERENCES 1. Schnell, J. R.; Chou, J. J. Structure and mechanism of the M2 proton channel of influenza A virus. Nature 2008, 451 (7178), 591-595. 2. Li, J.; Edwards, P. C.; Burghammer, M.; Villa, C.; Schertler, G. F. X. Structure of bovine rhodopsin in a trigonal crystal form. J. Mol. Biol. 2004, 343 (5), 1409-1438. 3. Ferguson, A. D.; McKeever, B. M.; Xu, S. H.; Wisniewski, D.; Miller, D. K.; Yamin, T. T.; Spencer, R. H.; Chu, L.; Ujjainwalla, F.; Cunningham, B. R.; Evans, J. F.; Becker, J. W. Crystal structure of inhibitor-bound human 5-lipoxygenaseactivating protein. Science 2007, 317 (5837), 510-512. 4. Belrhali, H.; Nollert, P.; Royant, A.; Menzel, C.; Rosenbusch, J. P.; Landau, E. M.; Pebay-Peyroula, E., Protein, lipid and water organization in bacteriorhodopsin crystals: a molecular view of the purple membrana at 1.9 angstrom resolution. Structure 1999, 7 (8), 909-917. 5. Vasilieva, L. G.; Fufina, T. Y.; Gabdulkhakov, A. G.; Leonova, M. M.; Khatypov, R. A.; Shuvalov, V. A. The sitedirected mutation I(L177)H in Rhodobacter sphaeroides reaction center affects coordination of P-A and B-B bacteriochlorophylls. Biochim. Biophys. Acta, Bioenerg. 2012, 1817 (8), 1407-1417. 6. Aller, S. G.; Yu, J.; Ward, A.; Weng, Y.; Chittaboina, S.; Zhuo, R. P.; Harrell, P. M.; Trinh, Y. T.; Zhang, Q. H.; Urbatsch, I. L.; Chang, G. Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding. Science 2009, 323 (5922), 1718-1722. 7. Hvorup, R. N.; Goetz, B. A.; Niederer, M.; Hollenstein, K.; Perozo, E.; Locher, K. P. Asymmetry in the structure of the ABC transporter-binding protein complex BtuCD-BtuF. Science 2007, 317 (5843), 1387-1390. 8. Lunin, V. V.; Dobrovetsky, E.; Khutoreskaya, G.; Zhang, R. G.; Joachimiak, A.; Doyle, D. A.; Bochkarev, A.; Maguire, M. E.; Edwards, A. M.; Koth, C. M. Crystal structure of the CorA Mg2+ transporter. Nature 2006, 440 (7085), 833-837. 9. Oldham, M. L.; Khare, D.; Quiocho, F. A.; Davidson, A. L.; Chen, J. Crystal structure of a catalytic intermediate of the maltose transporter. Nature 2007, 450 (7169), 515-521. 10. Jordan, P.; Fromme, P.; Witt, H. T.; Klukas, O.; Saenger, W.; Krauss, N. Three-dimensional structure of cyanobacterial photosystem I at 2.5 angstrom resolution. Nature 2001, 411 (6840), 909-917.
LAMBADA & InflateGRO2: Efficient Membrane Alignment and Insertion of Membrane Proteins for Molecular Dynamics Simulations
Thomas H. Schmidt, Christian Kandt* Computational Structural Biology, Department of Life Science Informatics B-IT, Life & Medical Sciences (LIMES) Center, University of Bonn, Dahlmannstr. 2, 53113 Bonn, Germany
Corresponding Author * Email: [email protected], Phone: #49 228 2699 324; Fax: #49 228 2699 341
Supplemental table 1: Additional set of LAMBADA test proteins Protein (PDB-ID)
Residues
TM Structure
Internal TM Cavity
Alignment time* + Orientation
Orientation deviation (compared to OPM)
Proton channel M2 (2RLF)1
152
Conical
Yes
6s
45 s
21.440°
Bovine rhodopsin (1GZM)2
328
Cylindrical
No
6s
2’ 27 s
12.945°
436
Cylindrical
Yes
6s
1’ 37 s
3.041°
684
Cylindrical
Yes
7s
3’ 23 s
0.014°
824
Irregular
No
8s
2’ 34 s
10.568°
P-glycoprotein (3G5U)6
1182
Conical
No
10 s
4’ 25 s
6.157°
Vitamin B12 transporter BtuCDF (2QI9)7
1389
Irregular
No
10 s
4’ 16 s
6.472°
CorA Mg2+ transporter (2BBJ)8
1670
Irregular
No
12 s
6’ 14 s
0.813°
Maltose (2R6G)9
1887
Irregular
No
12 s
6’ 21 s
6.284°
6729
Irregular
No
34 s
23’ 56 s
2.941°
5-lipoxygenase-activating (FLAP) (2Q7M)3
protein
Bacteriorhodopsin (1QHJ)4 Photosynthetic (3V3Y)5
reaction
transporter
Photosystem I (1JB0)10
center
MalGFK-E
*performed using a single core on a 4 GB RAM DELL Precision 390 workstation (CPU: Intel® Core™2 6700 2x2.66 GHz)
Supplemental figure 1: LAMBADA output for an additional set of ten membrane proteins of different size and transmembrane structure. For each protein the membrane-embedded LAMBADA prediction is compared to the corresponding entry in the orientation of proteins in membranes (OPM) database. Lipid head groups are colored in blue, charged proteins residues are red, hydrophobic residues appear white. For the LAMBADA results the protein’s hydrophobic belt region is highlighted in yellow. LAMBADA correctly aligns each test protein yielding either equivalent (1GZM, 2Q7M, 1QHJ, 3V3Y, 3G5U, 2QI9, 2BBJ, 2R6G, 1JB0) or better results (2RLF) compared to the OPM data base.
Supplemental figure 2: In three cases of the first set of nine test proteins the LAMBADA orientations differed between 9° and 10° from the predictions made by the orientation of protein in membrane (OPM) database. Comparing the OPM (left) and LAMBADA orientations (right) side by side, we find that for the outer membrane protein OmpX (PDB-ID: 1QJ9) (a) and the outer membrane phospholipase A (PDB-ID: 1QD5) (b), the LAMBADA prediction yields a better match between hydrophobic belt and lipid bilayer, whereas for the lipid A deacylase LpxR (PDB-ID: 3FID) (c) both orientations appear equally valid.
REFERENCES 1. Schnell, J. R.; Chou, J. J. Structure and mechanism of the M2 proton channel of influenza A virus. Nature 2008, 451 (7178), 591-595. 2. Li, J.; Edwards, P. C.; Burghammer, M.; Villa, C.; Schertler, G. F. X. Structure of bovine rhodopsin in a trigonal crystal form. J. Mol. Biol. 2004, 343 (5), 1409-1438. 3. Ferguson, A. D.; McKeever, B. M.; Xu, S. H.; Wisniewski, D.; Miller, D. K.; Yamin, T. T.; Spencer, R. H.; Chu, L.; Ujjainwalla, F.; Cunningham, B. R.; Evans, J. F.; Becker, J. W. Crystal structure of inhibitor-bound human 5-lipoxygenaseactivating protein. Science 2007, 317 (5837), 510-512. 4. Belrhali, H.; Nollert, P.; Royant, A.; Menzel, C.; Rosenbusch, J. P.; Landau, E. M.; Pebay-Peyroula, E., Protein, lipid and water organization in bacteriorhodopsin crystals: a molecular view of the purple membrana at 1.9 angstrom resolution. Structure 1999, 7 (8), 909-917. 5. Vasilieva, L. G.; Fufina, T. Y.; Gabdulkhakov, A. G.; Leonova, M. M.; Khatypov, R. A.; Shuvalov, V. A. The sitedirected mutation I(L177)H in Rhodobacter sphaeroides reaction center affects coordination of P-A and B-B bacteriochlorophylls. Biochim. Biophys. Acta, Bioenerg. 2012, 1817 (8), 1407-1417. 6. Aller, S. G.; Yu, J.; Ward, A.; Weng, Y.; Chittaboina, S.; Zhuo, R. P.; Harrell, P. M.; Trinh, Y. T.; Zhang, Q. H.; Urbatsch, I. L.; Chang, G. Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding. Science 2009, 323 (5922), 1718-1722. 7. Hvorup, R. N.; Goetz, B. A.; Niederer, M.; Hollenstein, K.; Perozo, E.; Locher, K. P. Asymmetry in the structure of the ABC transporter-binding protein complex BtuCD-BtuF. Science 2007, 317 (5843), 1387-1390. 8. Lunin, V. V.; Dobrovetsky, E.; Khutoreskaya, G.; Zhang, R. G.; Joachimiak, A.; Doyle, D. A.; Bochkarev, A.; Maguire, M. E.; Edwards, A. M.; Koth, C. M. Crystal structure of the CorA Mg2+ transporter. Nature 2006, 440 (7085), 833-837. 9. Oldham, M. L.; Khare, D.; Quiocho, F. A.; Davidson, A. L.; Chen, J. Crystal structure of a catalytic intermediate of the maltose transporter. Nature 2007, 450 (7169), 515-521. 10. Jordan, P.; Fromme, P.; Witt, H. T.; Klukas, O.; Saenger, W.; Krauss, N. Three-dimensional structure of cyanobacterial photosystem I at 2.5 angstrom resolution. Nature 2001, 411 (6840), 909-917.
