Molecular dynamics simulations of apocytochrome b(562) - The highly ordered limit of molten globules

被引:33
作者
Laidig, KE [1 ]
Daggett, V [1 ]
机构
[1] UNIV WASHINGTON,DEPT MED CHEM,SEATTLE,WA 98195
来源
FOLDING & DESIGN | 1996年 / 1卷 / 05期
关键词
apocytochrome b(562); folding intermediates; molecular dynamics; molten globule; sidechain mobility;
D O I
10.1016/S1359-0278(96)00049-1
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
Background: Cytochrome b(562) is a heme-containing, four-helix bundle. It has been proposed that the apo form of the protein is a molten globule. We present a molecular dynamics study of apocytochrome b(562) to investigate its structural and dynamic properties. Results: Our simulations suggest that all four helices are essentially intact and confirm that the experimental difficulties of assigning helical NOEs in the C-terminal helix are not due to structural disorder. The increased 'moltenness' of the apoprotein is due to an increased mobility of the sidechains. The small observed increase in compressibility for the apoprotein is proposed to be the result of an increase in the intrinsic protein compressibility, which is opposed by the increase in the size of the protein hydration shell. Conclusions: Apocytochrome b(562) is postulated to be near the highly ordered limit of the molten globule state, a structure whose molten character is due primarily to increased sidechain mobility with concurrent loss in tertiary contacts between the helices, rather than changes in the folding topology or substantially increased disorder of the secondary structure. (C) Current Biology Ltd
引用
收藏
页码:335 / 346
页数:12
相关论文
共 36 条
[1]   MOLECULAR-DYNAMICS SIMULATIONS OF PROTEIN UNFOLDING AND LIMITED REFOLDING - CHARACTERIZATION OF PARTIALLY UNFOLDED STATES OF UBIQUITIN IN 60-PERCENT METHANOL AND IN WATER [J].
ALONSO, DOV ;
DAGGETT, V .
JOURNAL OF MOLECULAR BIOLOGY, 1995, 247 (03) :501-520
[2]   CHARACTERIZATION OF A PARTLY FOLDED PROTEIN BY NMR METHODS - STUDIES ON THE MOLTEN GLOBULE STATE OF GUINEA-PIG ALPHA-LACTALBUMIN [J].
BAUM, J ;
DOBSON, CM ;
EVANS, PA ;
HANLEY, C .
BIOCHEMISTRY, 1989, 28 (01) :7-13
[3]   SIDE-CHAIN ENTROPY AND PACKING IN PROTEINS [J].
BROMBERG, S ;
DILL, KA .
PROTEIN SCIENCE, 1994, 3 (07) :997-1009
[4]   CHARACTERIZATION OF NATIVE APOMYOGLOBIN BY MOLECULAR-DYNAMICS SIMULATION [J].
BROOKS, CL .
JOURNAL OF MOLECULAR BIOLOGY, 1992, 227 (02) :375-380
[5]   A MODEL OF THE MOLTEN GLOBULE STATE FROM MOLECULAR-DYNAMICS SIMULATIONS [J].
DAGGETT, V ;
LEVITT, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (11) :5142-5146
[6]   MOLECULAR-DYNAMICS SIMULATIONS OF HELIX DENATURATION [J].
DAGGETT, V ;
LEVITT, M .
JOURNAL OF MOLECULAR BIOLOGY, 1992, 223 (04) :1121-1138
[7]   PROTEIN UNFOLDING PATHWAYS EXPLORED THROUGH MOLECULAR-DYNAMICS SIMULATIONS [J].
DAGGETT, V ;
LEVITT, M .
JOURNAL OF MOLECULAR BIOLOGY, 1993, 232 (02) :600-619
[8]   A MOLECULAR-DYNAMICS SIMULATION OF POLYALANINE - AN ANALYSIS OF EQUILIBRIUM MOTIONS AND HELIX COIL TRANSITIONS [J].
DAGGETT, V ;
KOLLMAN, PA ;
KUNTZ, ID .
BIOPOLYMERS, 1991, 31 (09) :1115-1134
[9]   EFFECT OF HEME BINDING ON THE STRUCTURE AND STABILITY OF ESCHERICHIA-COLI APOCYTOCHROME-B562 [J].
FENG, YQ ;
SLIGAR, SG .
BIOCHEMISTRY, 1991, 30 (42) :10150-10155
[10]   SOLUTION STRUCTURE OF APOCYTOCHROME B(562) [J].
FENG, YQ ;
SLIGAR, SG ;
WAND, AJ .
NATURE STRUCTURAL BIOLOGY, 1994, 1 (01) :30-35