Molecular Modeling of the Three-Dimensional Structure of Human Sphingomyelin Synthase CHEMISTRY D3325 A28 R3 Figure 5 The hSMs 1/SM complex structure as the last snapshot of 10 ns molecular dynamics simulation. (A) hSMSI is rendered in ribbons. Several key residues around SM are shown in stick models. Dashed lines stand for hydrogen bonds. (B)hSMSI is rendered in the solvent accessible surface. SM is rendered in stick model. The arrow indicates where the choline moiety on SM is buried inside Table 3 Computed binding energies between hSMSl and some lipid substrates Complex Binding energy/(k.mol) ASMSI/PE 62.80 hSMS1/PA hSMSI/PS 63.76 hSMSI/PG 32.80 The binding energy between hSMSI and SM is taken as the energy rererence. Table 4 Computed binding energies between hSMSl mutations and SM 180-135-90-5 hhSMS I mutation Binding energy/ (kJmol) Phi° Figure 6 Ramachandran plot of the structural model of hSMSI D332A after molecular dynamics refinement. A: core alpha; a: allowed H285A 26.27 alpha; -a: general alpha; B: core beta; b: allowed beta, -b: gen-H328A 73.47 eral beta; L: core left-handed alpha; I: allowed left-handed alpha, R342A -l: general left-handed alpha, p: allowed epsilon,-p: genera Y338A epsilon. Glycines are shown as triangles. Here, 87.5% of residues 21.08 are in the most favored regions(A, B, L), 10.5% of residues are in the additionally allowed regions(a, b, 1, p), 1.0% of residues H274A 18.95 are in the generally allowed regions (a, b, -1, -p), and only L281A 1.0% of residues are in the disallowed regions F173A 17.61 mode analysis(NMA) was conducted to analyze the F3A+1A+74A+1281A5414 ntrinsic motions of the hSMSl structure. The eINemo The binding energy between SMSI and SM is set as the refer on-lineserver(http://igs-server.cnrs-mrs.fr/elnemo/ence Chin J. Chem. 2011, 29, 1567--1575 C2011 SIOC, CAS, Shanghai, WILEY-VCH Verlag gmbH Co KGaA, Weinheim wweje. wiley-vch.de 15Molecular Modeling of the Three-Dimensional Structure of Human Sphingomyelin Synthase Chin. J. Chem. 2011, 29, 1567—1575 © 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.cjc.wiley-vch.de 1571 Figure 5 The hSMS1/SM complex structure as the last snapshot of 10 ns molecular dynamics simulation. (A) hSMS1 is rendered in ribbons. Several key residues around SM are shown in stick models. Dashed lines stand for hydrogen bonds. (B) hSMS1 is rendered in the solvent accessible surface. SM is rendered in stick model. The arrow indicates where the choline moiety on SM is buried inside. Figure 6 Ramachandran plot of the structural model of hSMS1 after molecular dynamics refinement. A: core alpha; a: allowed alpha; ~a: general alpha; B: core beta; b: allowed beta; ~b: gen￾eral beta; L: core left-handed alpha; l: allowed left-handed alpha; ~l: general left-handed alpha; p: allowed epsilon; ~p: general epsilon. Glycines are shown as triangles. Here, 87.5% of residues are in the most favored regions (A, B, L), 10.5% of residues are in the additionally allowed regions (a, b, l, p), 1.0% of residues are in the generally allowed regions (~a, ~b, ~l, ~p), and only 1.0% of residues are in the disallowed regions. mode analysis (NMA) was conducted to analyze the intrinsic motions of the hSMS1 structure. The elNémo on-line server (http://igs-server.cnrs-mrs.fr/elnemo/ Table 3 Computed binding energies between hSMS1 and some lipid substrates Complex Binding energy/(kJ•mol－1 ) hSMS1/SM 0.00a hSMS1/PC －27.90 hSMS1/PE 62.80 hSMS1/PA 123.80 hSMS1/PS 63.76 hSMS1/PG 32.80 a The binding energy between hSMS1 and SM is taken as the energy reference. Table 4 Computed binding energies between hSMS1 mutations and SM hhSMS1 mutation Binding energy/(kJ•mol－1 ) Wild type 0.00a D332A －0.25 H285A 26.27 H328A 73.47 R342A 81.79 Y338A 21.08 F177A 7.57 H274A 18.95 L281A 14.60 F173A 17.61 F173A＋F177A＋H274A＋L281A 54.14 a The binding energy between SMS1 and SM is set as the refer￾ence