Hydrophobicity maps of the N-peptide coiled coil of HIV-1 gp41

被引:28
作者
Siebert, X [1 ]
Hummer, G [1 ]
机构
[1] NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1021/bi0158526
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Blocking HIV-1 viral entry into the host cell offers a promising new, strategy for interfering with the HIV-1 life cycle. A major target of inhibitor design is to prevent binding of fusogenic gp41 C-peptides to the trimeric coiled coil of fusion-active N-peptides. Here, we map the hydrophobic character of the binding surface of the IQN17 peptide, a soluble analogue of the N-peptide coiled coil. The local binding affinity for a hydrophobic probe is determined by three methods: a hydrophobic force field, and molecular dynamics in solution analyzed by test particle insertion and inhomogeneous information theory. The regions of highest calculated hydrophobicity overlap with the positions of the hydrophobic anchor residues of the native C-peptides, and of two known inhibitors. Additional binding sites not exploited by these inhibitors are identified, and modifications for enhancing their binding affinity are suggested.
引用
收藏
页码:2956 / 2961
页数:6
相关论文
共 76 条
[1]   An experimental approach to mapping the binding surfaces of crystalline proteins [J].
Allen, KN ;
Bellamacina, CR ;
Ding, XC ;
Jeffery, CJ ;
Mattos, C ;
Petsko, GA ;
Ringe, D .
JOURNAL OF PHYSICAL CHEMISTRY, 1996, 100 (07) :2605-2611
[2]   Entropy of hydrophobic hydration: Extension to hydrophobic chains [J].
Ashbaugh, HS ;
Paulaitis, ME .
JOURNAL OF PHYSICAL CHEMISTRY, 1996, 100 (05) :1900-1913
[3]  
Berendsen H., 1981, INTERMOLECULAR FORCE, V331, P331, DOI [DOI 10.1007/978-94-015-7658-1_21, 10.1007/978-94-015-7658, DOI 10.1007/978-94-015-7658]
[4]   MOLECULAR-DYNAMICS WITH COUPLING TO AN EXTERNAL BATH [J].
BERENDSEN, HJC ;
POSTMA, JPM ;
VANGUNSTEREN, WF ;
DINOLA, A ;
HAAK, JR .
JOURNAL OF CHEMICAL PHYSICS, 1984, 81 (08) :3684-3690
[5]  
Bliznyuk AA, 1999, J COMPUT CHEM, V20, P983, DOI 10.1002/(SICI)1096-987X(19990715)20:9<983::AID-JCC9>3.0.CO
[6]  
2-R
[7]   STRUCTURE OF INFLUENZA HEMAGGLUTININ AT THE PH OF MEMBRANE-FUSION [J].
BULLOUGH, PA ;
HUGHSON, FM ;
SKEHEL, JJ ;
WILEY, DC .
NATURE, 1994, 371 (6492) :37-43
[8]   Three-dimensional solution structure of the 44 kDa ectodomain of SIV gp41 [J].
Caffrey, M ;
Cai, ML ;
Kaufman, J ;
Stahl, SJ ;
Wingfield, PT ;
Covell, DG ;
Gronenborn, AM ;
Clore, GM .
EMBO JOURNAL, 1998, 17 (16) :4572-4584
[9]   Hydration structure of the α-chymotrypsin substrate binding pocket:: the impact of constrained geometry [J].
Carey, C ;
Cheng, YK ;
Rossky, PJ .
CHEMICAL PHYSICS, 2000, 258 (2-3) :415-425
[10]  
Carlson HA, 2000, MOL PHARMACOL, V57, P213