MOLECULAR MODELING OF CONFORMATIONS OF NON TRIPLE HELICAL REGIONS OF COLLAGEN
MOLECULAR MODELING OF CONFORMATIONS OF NON TRIPLE HELICAL REGIONS OF COLLAGEN
批准号:
6456775
负责人:
RAJENDRA S BHATNAGAR
金额:
$27.32万
依托单位国家:
美国
项目类别:
财政年份:
2001
资助国家:
美国
项目状态:
已结题
起止时间:
2001-07-01 至 2003-08-31
中文摘要
我们正在研究一个分子的构象趋势
I型胶原蛋白的α1(I)链中缺乏亚氨基的序列。
序列GTPGPQGIAGQRGVV,这里称为P15,显示了
偏离三螺旋多聚Pro-II(PpII)的倾向
构象。我们之前的研究表明,这个地区有一个
倾向于采用GIAG处于Beta弯的构象
构象,两侧是延伸构象中的两个区域。这
是与整合素结合时最有可能采用的构象。
与胶原酶络合的抑制剂的X射线结构表明
胶原酶的裂解部位GIAG区域处于
当与这种酶结合时,延长的构象。的构象
在与胶原酶结合期间,GIAG片段两侧的区域为
未知。因此,我们正在研究P15区域的构象
胶原蛋白中的趋势,以开发I型胶原如何
胶原蛋白与胶原酶相互作用。分子的构象趋势
与胶原蛋白-胶原酶复合体相关的胶原蛋白
胶原酶抑制剂用于肿瘤预防的设计
转移。我们正在进行分子动力学(MD)计算
胶原蛋白三螺旋结构中的P15区域。为了增强
构象采样,我们还结合了多克隆
MD(MMD)算法转化为琥珀。从这些衍生出来的构象
模拟将用于胶原酶的对接研究。
MidasPlus与加州大学旧金山分校计算机图形实验室的设施
已用于图形建模和可视化
分子几何,用于制备制备起始结构
模拟,用于监视模拟。
英文摘要
We are investigating the conformational tendencies of an
imino-poor sequence within the alpha1(I) chain of type I collagen.
The sequence GTPGPQGIAGQRGVV, referred to here as P15, shows a
tendency to deviate from the triple-helical polyproline-II (ppII)
conformation. Our previous studies suggest that this region has a
tendency to adopt a conformation in which GIAG is in a beta-bend
conformation, flanked by two regions in extended conformations. This
is the most likely conformation adopted when bound to integrins.
X-ray structures of inhibitors complexed with collagenase suggest that
the GIAG region, which is the site of collagenase cleavage, is in an
extended conformation when bound to this enzyme. The conformation of
regions flanking the GIAG segment during binding to collagenase are
unknown. We are thus examining the P15 region's conformational
tendencies within collagen, in order to develop a model of how type I
collagen interacts with collagenase. The conformational tendencies of
collagen, as related to the collagen-collagenase complex, are relevant
to the design of collagenase inhibitors for the prevention of tumor
metastasis. We are performing molecular dynamics (MD) calculations on
the P15 region within the collagen triple-helix. To enhance
conformational sampling, we are also incorporating the multicanonical
MD (MMD) algorithm into AMBER. Conformations derived from these
simulations will be used in docking studies with collagenase.
MidasPlus and the facilities of the UCSF Computer Graphics Laboratory
have been used for graphical modeling and visualization of the
molecular geometry, for preparing preparing starting structures for
simulations, for monitoring the simulations.
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Biomaterials for Orbit Reconstruction
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批准号:6338028
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项目类别:
-
资助金额:$10.0万
-
财政年份:2001
-
负责人:RAJENDRA S BHATNAGAR
-
依托单位:
MOLECULAR MODELING OF CONFORMATIONS OF NON TRIPLE HELICAL REGIONS OF COLLAGEN
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批准号:6347937
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项目类别:
-
资助金额:$0.01万
-
财政年份:2000
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负责人:RAJENDRA S BHATNAGAR
-
依托单位:
NOVEL SCAFFOLDS FOR BLADDER REPAIR
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批准号:6298910
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项目类别:
-
资助金额:$10.0万
-
财政年份:2000
-
负责人:RAJENDRA S BHATNAGAR
-
依托单位:
MOLECULAR MODELING OF CONFORMATIONS OF NON TRIPLE HELICAL REGIONS OF COLLAGEN
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批准号:6220307
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项目类别:
-
资助金额:$0.01万
-
财政年份:1999
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负责人:RAJENDRA S BHATNAGAR
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依托单位:
BIOMATERIALS FOR PERIODONTAL TISSUE RESTORATION
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批准号:2132996
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项目类别:
-
资助金额:$9.96万
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财政年份:1996
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负责人:RAJENDRA S BHATNAGAR
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依托单位:
MOLECULAR BASIS OF COLLAGEN REACTIVITY
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批准号:3157996
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项目类别:
-
资助金额:$15.53万
-
财政年份:1986
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负责人:RAJENDRA S BHATNAGAR
-
依托单位:
MOLECULAR BASIS OF COLLAGEN REACTIVITY
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批准号:3157992
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项目类别:
-
资助金额:$15.55万
-
财政年份:1986
-
负责人:RAJENDRA S BHATNAGAR
-
依托单位:
MOLECULAR BASIS OF COLLAGEN REACTIVITY
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批准号:3157995
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项目类别:
-
资助金额:$15.19万
-
财政年份:1986
-
负责人:RAJENDRA S BHATNAGAR
-
依托单位:
MOLECULAR BASIS OF COLLAGEN REACTIVITY
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批准号:3157997
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项目类别:
-
资助金额:$16.42万
-
财政年份:1986
-
负责人:RAJENDRA S BHATNAGAR
-
依托单位:
UCSF/UCB BIOENGINEERING GRADUATE PROGRAM
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批准号:2167383
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项目类别:
-
资助金额:$13.57万
-
财政年份:1985
-
负责人:RAJENDRA S BHATNAGAR
-
依托单位:
UCSF/UCB BIOENGINEERING GRADUATE PROGRAM
-
批准号:3538182
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项目类别:
-
资助金额:$10.98万
-
财政年份:1985
-
负责人:RAJENDRA S BHATNAGAR
-
依托单位:
UCSF/UCB BIOENGINEERING GRADUATE PROGRAM
-
批准号:3538183
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项目类别:
-
资助金额:$12.98万
-
财政年份:1985
-
负责人:RAJENDRA S BHATNAGAR
-
依托单位:
UCSF/UCB BIOENGINEERING GRADUATE PROGRAM
-
批准号:3538180
-
项目类别:
-
资助金额:$9.45万
-
财政年份:1985
-
负责人:RAJENDRA S BHATNAGAR
-
依托单位:
UCSF/UCB BIOENGINEERING GRADUATE PROGRAM
-
批准号:3538179
-
项目类别:
-
资助金额:$5.6万
-
财政年份:1985
-
负责人:RAJENDRA S BHATNAGAR
-
依托单位:
UCSF/UCB BIOENGINEERING GRADUATE PROGRAM
-
批准号:2167384
-
项目类别:
-
资助金额:$14.41万
-
财政年份:1985
-
负责人:RAJENDRA S BHATNAGAR
-
依托单位:
UCSF/UCB BIOENGINEERING GRADUATE PROGRAM
-
批准号:3538178
-
项目类别:
-
资助金额:$12.33万
-
财政年份:1985
-
负责人:RAJENDRA S BHATNAGAR
-
依托单位:
UCSF/UCB BIOENGINEERING GRADUATE PROGRAM
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批准号:3538177
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项目类别:
-
资助金额:$2.8万
-
财政年份:1985
-
负责人:RAJENDRA S BHATNAGAR
-
依托单位:
UCSF/UCB BIOENGINEERING GRADUATE PROGRAM
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批准号:3538184
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项目类别:
-
资助金额:$10.57万
-
财政年份:1985
-
负责人:RAJENDRA S BHATNAGAR
-
依托单位:
UCSF/UCB BIOENGINEERING GRADUATE PROGRAM
-
批准号:3538181
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项目类别:
-
资助金额:$9.52万
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财政年份:1985
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负责人:RAJENDRA S BHATNAGAR
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依托单位:
MOLECULAR MODELLING OF CONFORMATIONS OF COLLAGEN DERIVED CELL ADHESION PEPTIDES
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批准号:5222434
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:RAJENDRA S BHATNAGAR
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依托单位:--
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