Supplementary Material for
Molecular Mechanism of the Selectivity between BAFF/APRIL and Their Receptors by Molecular Simulations
Xuegang Fu †,a, Zhuo Mao †,a, Siming Li a, Yunyun Guan a, Xiaodong Jian b, Jian Sun *,a, Jing Wei *,a
aTianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072, P. R. China
bNational Supercomputing Center in Tianjin, 3F, No.5 Building, TEDA Service Outsourcing Industrial Park, Binhai New Area, Tianjin, 300457, P. R. China
†These authors contribute equally to this work
This file includes:
Figure S1 The alignment of the BAFF, murine and human APRIL 1
Figure S2 Time dependence of RMSD values along the MD trajectories for each system 2
Figure S3 Time dependence of RMSD values along the MD trajectories for BAFF-BCMA system 3
Figure S4 Time dependence of RMSD values along the MD trajectories for BAFF-TACI1 system 4
Figure S5 Time dependence of RMSD values along the MD trajectories for BAFF-TACI2 system 5
Figure S6 Time dependence of RMSD values along the MD trajectories for BAFF-BR3 system 6
Figure S7 Time dependence of RMSD values along the MD trajectories for APRIL-BCMA system 7
Figure S8 Time dependence of RMSD values along the MD trajectories for APRIL-TACI1 system 8
Figure S9 Time dependence of RMSD values along the MD trajectories for APRIL-TACI2 system 9
Figure S10 Ramachandran plot of the best rational APRIL and TACI1 model 9
Figure S11 Time dependence of ΔG (the binding energy) values of each system during last ns 10
Table S1 Distances between hydrogen bond donor and acceptor for BAFF in BAFF-Rec system 11
Table S2 Distances between hydrogen bond donor and acceptor for APRIL in APRIL-Rec system 11
Table S3 The number of amino acids of N- and C- loop of TNF receptors 11
APPENDIX Specific options of GB methods for binding free energy calculation 12
Figure S1. The alignment of the BAFF, murine and human APRIL. The bar denotes β-strands. Strands are labelled as following: A, a, a’, A’’, B, B’, C, D, E, F, G, and H. The two antiparallel sheets form the jellyroll: one sheet consists of strands A’’, A, H, C and F, and the other sheet consists of strands B’, B, G, D and E.
Figure S2 Time dependence of RMSD values along the MD trajectories for backbone atoms (Cα, C and N atoms) of each system. (A) BAFF-BCMA, (B) BAFF-TACI1, (C) BAFF-TACI2, (D) BAFF-BR3, (E) APRIL-BCMA, (F) APRIL-TACI1, and (G) APRIL-TACI2 complex.
Figure S3 Time dependence of RMSD values along the MD trajectories for backbone atoms (Cα, C and N atoms) of BAFF-BCMA system.
Figure S4 Time dependence of RMSD values along the MD trajectories for backbone atoms (Cα, C and N atoms) of BAFF-TACI1 system.
Figure S5 Time dependence of RMSD values along the MD trajectories for backbone atoms (Cα, C and N atoms) of BAFF-TACI2 system.
Figure S6 Time dependence of RMSD values along the MD trajectories for backbone atoms (Cα, C and N atoms) of BAFF-BR3 system.
Figure S7 Time dependence of RMSD values along the MD trajectories for backbone atoms (Cα, C and N atoms) of APRIL-BCMA system.
Figure S8 Time dependence of RMSD values along the MD trajectories for backbone atoms (Cα, C and N atoms) of APRIL-TACI1 system.
Figure S9 Time dependence of RMSD values along the MD trajectories for backbone atoms (Cα, C and N atoms) of APRIL-TACI2 system.
Figure S10. Ramachandran plot of the best rational APRIL (A) and TACI1 (B) model.
Figure S11. Time dependence of ΔG (the binding energy) values of each system during last ns. (A) BAFF-BCMA, (B) BAFF-TACI1, (C) BAFF-TACI2, (D) BAFF-BR3, (E) APRIL-BCMA, (F) APRIL-TACI1, and (G) APRIL-TACI2 complex.
Table S1. Distances (Å) between hydrogen bond donor and acceptor for BAFF in BAFF-Rec system (donor–acceptor)
BAFF-BCMA / 3.09 ± 0.07 / 2.88 ± 0.07 / 4.24 ± 0.96
BAFF-TACI1 / 3.19 ± 0.07 / 2.83 ± 0.08 / 3.86 ± 0.72
BAFF-TACI2 / 3.01 ± 0.23 / 2.77 ± 0.04 / 4.38 ± 0.17
BAFF-BR3 / 3.22 ± 0.29 / 2.65 ± 0.11 / 3.19 ± 0.73
a The data are in “mean value ± stand deviation” form.
Table S2. Distances (Å) between hydrogen bond donor and acceptor for APRIL in APRIL-Rec system (donor–acceptor)
System / S103 N–I92 O (Å) a / S106 OG–Q57 OE1 (Å) a / R90 NH1–H134 ND1 (Å) aAPRIL-BCMA / 3.20 ± 0.27 / 2.65 ± 0.02 / 4.26 ± 0.99
APRIL-TACI1 / 3.09 ± 0.35 / 2.66 ± 0.11 / 4.69 ± 0.58
APRIL-TACI2 / 2.91 ± 0.10 / 2.72 ± 0.13 / 3.97 ± 0.59
a The data are in “mean value ± stand deviation” form.
Table S3. The number of amino acids of N- and C- loop of TNF receptors
TNF receptor / Total length / N- loop length / C- loop length / Proportion of loop lengthBR3 / 31 / 8 / 13 / 67.74%
BCMA / 39 / 4 / 3 / 17.95%
TACI1 / 36 / 6 / 1 / 19.44%
TACI2 / 36 / 6 / 2 / 22.22%
APPENDIX: Specific options of GB methods for binding free energy calculation
l IGB = 2; Switches between Onufriev's GB.
l GBSA = 1; Switches between LCPO method for SASA calc.
l SALTCON = 0.00; Concentration (in M) of 1-1 mobile counterions in solution.
l EXTDIEL = 80.0; Dielectricity constant for the solvent.
l INTDIEL = 1.0; Dielectricity constant for the solute
l SURFTEN = 0.0072, SURFOFF = 0.00; SURFTEN/SURFOFF Values used to compute the nonpolar contribution ΔGNP to the desolvation according to ΔGNP = SURFTEN * SASA + SURFOFF.
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