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Molecular docking simulations for i
Molecular docking simulations for in silico virtual design of a
small molecule PPI inhibitor
Molecular docking simulations were conducted using the Glide
module in Maestro 9.8 (Schrodinger Inc., Cambridge, MA, USA)
under ligand-flexible mode [33]. The starting structure of IPS-
02001 was prepared from the Builder module in Maestro software. The co-crystal structure of integrin and the RGD peptide
ligand was obtained from the Protein Data Bank (PDB id 1L5G). The
initial receptor structure was prepared by deleting the authentic
cyclic RGD-peptide ligand. The molecular grid was defined for
integrin using the Receptor Grid Generation tool in Glide with the
25 Å cubic box. Molecular docking was conducted under the extra
precision XP mode with the Glide XP 5.0 scoring function to obtain
accurate binding mode and affinity data. In this docking mode, a
0.5 kcal/mol energy window and distance-dependent dielectric
constant ( 3¼ 1) were applied to the sampling process. The 10 most
docked poses were recorded throughout the docking process.
2.2. ProteoChip-based integrin avb3eOPN interaction assay
Recombinant integrin avb3 (100 mg/ml in 10 mM octyl-b-D-glucopyranoside, 1 mM CaCl2, 1 mM MgCl2, and 30% glycerol in PBS as
buffer) was immobilized onto the ProteoChip for 16 h at 4 C as a
capture protein. After washing twice with 0.05% PBST for 10 min
and drying under N2 gas, the ProteoChip was blocked with 3% BSA
for 1 h at room temperature. The ProteoChip was washed three
times with PBST and dried. Next, fluorescent dye (Cy5)-labeled OPN
was applied to the ProteoChip at concentrations ranging from 0 to
10 mg/ml in PBS containing 10 mM octyl-b-D-glucopyranoside,
1 mM CaCl2, 1 mM MgCl2, and 30% glycerol and then incubated for
1 h at 37 C. To assess inhibitor screening, Cy5-labeled OPN (0.8 mg/
ml in 10 mM octyl-b-D-glucopyranoside, 1 mM CaCl2, 1 mM MgCl2,
and 30% glycerol in PBS) and the compounds obtained from in silico
virtual screening were applied to the ProteoChip and incubated for
1 h at 37 C. The ProteoChip was washed with PBST and distilled
water, and dried under N2 gas. Next, the compounds were dissolved
in 100% DMSO and diluted to the desired concentrations in 10 mM
octyl-b-D-glucopyranoside, 1 mM CaCl2, 1 mM MgCl2, and 30%
glycerol in PBS. The diluted compounds and OPN were further
diluted to 100 mM with 10 mM octyl-b-D-glucopyranoside, 1 mM
CaCl2, 1 mM MgCl2, and 30% glycerol in PBS and spotted onto the
integrin avb3 array of the ProteoChip. The inhibitor concentrations
small molecule PPI inhibitor
Molecular docking simulations were conducted using the Glide
module in Maestro 9.8 (Schrodinger Inc., Cambridge, MA, USA)
under ligand-flexible mode [33]. The starting structure of IPS-
02001 was prepared from the Builder module in Maestro software. The co-crystal structure of integrin and the RGD peptide
ligand was obtained from the Protein Data Bank (PDB id 1L5G). The
initial receptor structure was prepared by deleting the authentic
cyclic RGD-peptide ligand. The molecular grid was defined for
integrin using the Receptor Grid Generation tool in Glide with the
25 Å cubic box. Molecular docking was conducted under the extra
precision XP mode with the Glide XP 5.0 scoring function to obtain
accurate binding mode and affinity data. In this docking mode, a
0.5 kcal/mol energy window and distance-dependent dielectric
constant ( 3¼ 1) were applied to the sampling process. The 10 most
docked poses were recorded throughout the docking process.
2.2. ProteoChip-based integrin avb3eOPN interaction assay
Recombinant integrin avb3 (100 mg/ml in 10 mM octyl-b-D-glucopyranoside, 1 mM CaCl2, 1 mM MgCl2, and 30% glycerol in PBS as
buffer) was immobilized onto the ProteoChip for 16 h at 4 C as a
capture protein. After washing twice with 0.05% PBST for 10 min
and drying under N2 gas, the ProteoChip was blocked with 3% BSA
for 1 h at room temperature. The ProteoChip was washed three
times with PBST and dried. Next, fluorescent dye (Cy5)-labeled OPN
was applied to the ProteoChip at concentrations ranging from 0 to
10 mg/ml in PBS containing 10 mM octyl-b-D-glucopyranoside,
1 mM CaCl2, 1 mM MgCl2, and 30% glycerol and then incubated for
1 h at 37 C. To assess inhibitor screening, Cy5-labeled OPN (0.8 mg/
ml in 10 mM octyl-b-D-glucopyranoside, 1 mM CaCl2, 1 mM MgCl2,
and 30% glycerol in PBS) and the compounds obtained from in silico
virtual screening were applied to the ProteoChip and incubated for
1 h at 37 C. The ProteoChip was washed with PBST and distilled
water, and dried under N2 gas. Next, the compounds were dissolved
in 100% DMSO and diluted to the desired concentrations in 10 mM
octyl-b-D-glucopyranoside, 1 mM CaCl2, 1 mM MgCl2, and 30%
glycerol in PBS. The diluted compounds and OPN were further
diluted to 100 mM with 10 mM octyl-b-D-glucopyranoside, 1 mM
CaCl2, 1 mM MgCl2, and 30% glycerol in PBS and spotted onto the
integrin avb3 array of the ProteoChip. The inhibitor concentrations
0/5000
在硅虚拟设计的分子对接模拟小分子 PPI 抑制剂使用滑动进行了分子对接模拟在大师 9.8 （薛定谔 Inc.，美国马萨诸塞州，剑桥市） 模块根据配体灵活模式 [33]。起始结构的 IPS-02001 制得大师软硬件中的生成器模块。共晶结构整合素与 RGD 多肽配体得到了从蛋白质数据银行 (PDB id 1L5G)。的初始的受体结构，制得删去原汁原味循环的 RGD 肽配体。为定义分子网格整合素在滑翔与使用受体网格生成工具25 Å 立方盒。分子对接进行额外的下在滑翔 XP 5.0 打分函数获得精密 XP 模式数据准确绑定模式和亲和力。在此对接的模式下，0.5 千卡/摩尔能源窗口和距离依赖介质常数 (3 1) 被适用于采样过程。10 个之最在整个对接过程录得靠码头的姿势。2.2.基于 ProteoChip 的整合素 avb3eOPN 相互作用检测重组整合素 avb3 （100 毫克/毫升 10 毫米辛基-b-D-葡萄糖 copyranoside、 1 毫米 CaCl2、 MgCl2，1 毫米和 30%甘油的 PBS 为缓冲区） 在 4 C 作为固定化为 16 h ProteoChip捕获蛋白质。后两次与 0.05%洗 PBST 10 分钟而在 N2 气下烘干，ProteoChip 被阻止与 3%牛血清白蛋白在室温的 1 小时。ProteoChip 被冲走三用 PBST 倍和干燥。接下来，荧光染料 (Cy5)-标记 OPN适用于在浓度范围从 0 到 ProteoChip10 毫克/毫升中含 10 毫米辛基-b-D-吡喃葡萄糖苷，PBS1 毫米 CaCl2、 MgCl2，1 毫米和 30%的甘油，然后孵化为37 ℃ 1 h要评估抑制剂的筛选，Cy5 标记 OPN (0.8 毫克 /在辛基-b-D-吡喃葡萄糖苷 10 毫米，1 毫米 CaCl2，1 毫米 MgCl2，毫升和 30%甘油的 PBS） 和所得在硅化合物虚拟筛选被应用于 ProteoChip 和培养37 ℃ 1 hProteoChip 是用 PBST 洗涤和蒸馏水，并在 N2 气下晒干。接下来，这些化合物被溶化在 100%二甲基亚砜和稀释至所需浓度在 10 毫米辛基-b-D-吡喃葡萄糖苷、 1 毫米 CaCl2、 MgCl2，1 毫米和 30%在 PBS 中的甘油。稀释后的化合物和 OPN 是进一步被稀释到 100 毫米，10 毫米辛基-b-D-吡喃葡萄糖苷，1 毫米在 PBS 中的 CaCl2、 MgCl2，1 毫米和 30%甘油、 斑点上整合素的 ProteoChip avb3 数组。抑制剂浓度
正在翻譯中..
Molecular docking simulations for in silico virtual design of a
small molecule PPI inhibitor
Molecular docking simulations were conducted using the Glide
module in Maestro 9.8 (Schrodinger Inc., Cambridge, MA, USA)
under ligand-flexible mode [33]. The starting structure of IPS-
02001 was prepared from the Builder module in Maestro software. The co-crystal structure of integrin and the RGD peptide
ligand was obtained from the Protein Data Bank (PDB id 1L5G). The
initial receptor structure was prepared by deleting the authentic
cyclic RGD-peptide ligand. The molecular grid was defined for
integrin using the Receptor Grid Generation tool in Glide with the
25 Å cubic box. Molecular docking was conducted under the extra
precision XP mode with the Glide XP 5.0 scoring function to obtain
accurate binding mode and affinity data. In this docking mode, a
0.5 kcal/mol energy window and distance-dependent dielectric
constant ( 3¼ 1) were applied to the sampling process. The 10 most
docked poses were recorded throughout the docking process.
2.2. ProteoChip-based integrin avb3eOPN interaction assay
Recombinant integrin avb3 (100 mg/ml in 10 mM octyl-b-D-glucopyranoside, 1 mM CaCl2, 1 mM MgCl2, and 30% glycerol in PBS as
buffer) was immobilized onto the ProteoChip for 16 h at 4 C as a
capture protein. After washing twice with 0.05% PBST for 10 min
and drying under N2 gas, the ProteoChip was blocked with 3% BSA
for 1 h at room temperature. The ProteoChip was washed three
times with PBST and dried. Next, fluorescent dye (Cy5)-labeled OPN
was applied to the ProteoChip at concentrations ranging from 0 to
10 mg/ml in PBS containing 10 mM octyl-b-D-glucopyranoside,
1 mM CaCl2, 1 mM MgCl2, and 30% glycerol and then incubated for
1 h at 37 C. To assess inhibitor screening, Cy5-labeled OPN (0.8 mg/
ml in 10 mM octyl-b-D-glucopyranoside, 1 mM CaCl2, 1 mM MgCl2,
and 30% glycerol in PBS) and the compounds obtained from in silico
virtual screening were applied to the ProteoChip and incubated for
1 h at 37 C. The ProteoChip was washed with PBST and distilled
water, and dried under N2 gas. Next, the compounds were dissolved
in 100% DMSO and diluted to the desired concentrations in 10 mM
octyl-b-D-glucopyranoside, 1 mM CaCl2, 1 mM MgCl2, and 30%
glycerol in PBS. The diluted compounds and OPN were further
diluted to 100 mM with 10 mM octyl-b-D-glucopyranoside, 1 mM
CaCl2, 1 mM MgCl2, and 30% glycerol in PBS and spotted onto the
integrin avb3 array of the ProteoChip. The inhibitor concentrations
small molecule PPI inhibitor
Molecular docking simulations were conducted using the Glide
module in Maestro 9.8 (Schrodinger Inc., Cambridge, MA, USA)
under ligand-flexible mode [33]. The starting structure of IPS-
02001 was prepared from the Builder module in Maestro software. The co-crystal structure of integrin and the RGD peptide
ligand was obtained from the Protein Data Bank (PDB id 1L5G). The
initial receptor structure was prepared by deleting the authentic
cyclic RGD-peptide ligand. The molecular grid was defined for
integrin using the Receptor Grid Generation tool in Glide with the
25 Å cubic box. Molecular docking was conducted under the extra
precision XP mode with the Glide XP 5.0 scoring function to obtain
accurate binding mode and affinity data. In this docking mode, a
0.5 kcal/mol energy window and distance-dependent dielectric
constant ( 3¼ 1) were applied to the sampling process. The 10 most
docked poses were recorded throughout the docking process.
2.2. ProteoChip-based integrin avb3eOPN interaction assay
Recombinant integrin avb3 (100 mg/ml in 10 mM octyl-b-D-glucopyranoside, 1 mM CaCl2, 1 mM MgCl2, and 30% glycerol in PBS as
buffer) was immobilized onto the ProteoChip for 16 h at 4 C as a
capture protein. After washing twice with 0.05% PBST for 10 min
and drying under N2 gas, the ProteoChip was blocked with 3% BSA
for 1 h at room temperature. The ProteoChip was washed three
times with PBST and dried. Next, fluorescent dye (Cy5)-labeled OPN
was applied to the ProteoChip at concentrations ranging from 0 to
10 mg/ml in PBS containing 10 mM octyl-b-D-glucopyranoside,
1 mM CaCl2, 1 mM MgCl2, and 30% glycerol and then incubated for
1 h at 37 C. To assess inhibitor screening, Cy5-labeled OPN (0.8 mg/
ml in 10 mM octyl-b-D-glucopyranoside, 1 mM CaCl2, 1 mM MgCl2,
and 30% glycerol in PBS) and the compounds obtained from in silico
virtual screening were applied to the ProteoChip and incubated for
1 h at 37 C. The ProteoChip was washed with PBST and distilled
water, and dried under N2 gas. Next, the compounds were dissolved
in 100% DMSO and diluted to the desired concentrations in 10 mM
octyl-b-D-glucopyranoside, 1 mM CaCl2, 1 mM MgCl2, and 30%
glycerol in PBS. The diluted compounds and OPN were further
diluted to 100 mM with 10 mM octyl-b-D-glucopyranoside, 1 mM
CaCl2, 1 mM MgCl2, and 30% glycerol in PBS and spotted onto the
integrin avb3 array of the ProteoChip. The inhibitor concentrations
正在翻譯中..
分子对接模拟在一个硅片上的虚拟设计小分子PPI抑制剂分子对接模拟进行了使用滑翔在大师9.8模块（薛定谔公司，剑桥马，美国）在配体柔性模式[ 33 ]。IPS的启动结构—02001是从大师的软洁具Builder模块编写。整合素的共晶结构和RGD肽从蛋白质数据银行得到了配体（PDB ID 1l5g）。这个初始受体结构的制备通过删除真实RGD环肽配体。分子网格被定义为整合使用受体网格生成工具在滑翔与25Å立方盒。分子对接下进行额外的与滑翔XP 5打分函数的精度获得XP模式精确的结合模式和亲和力数据。在这种对接模式下0.5千卡/摩尔能量窗口和距离相关的电介质恒（3¼1）进行采样过程。10最对接姿势记录在整个对接过程。2.2。基于整合素相互作用分析avb3eopn ProteoChip重组整合素avb3（100毫克/毫升10毫米octyl-b-d-glucopyranoside，氯化钙1毫米，1毫米氯化镁，30%甘油PBS缓冲）固定于ProteoChip 16小时4℃为捕获蛋白。0.05% PBST洗两次10分钟后在干燥的氮气，ProteoChip用3% BSA封闭在室温下1小时。该ProteoChip洗涤三次PBST和干。其次，荧光染料（Cy5）标记的OPN在浓度范围从0到应用于ProteoChip10毫克/毫升PBS含10毫米octyl-b-d-glucopyranoside，氯化钙1毫米，1毫米和30%氯化镁，甘油和孵育1小时在37 C.评估抑制剂筛选，Cy5标记的OPN（0.8毫克/octyl-b-d-glucopyranoside毫升10毫米，1毫米1毫米CaCl2、MgCl2，30%甘油PBS）和得到的化合物在硅片虚拟筛选应用于ProteoChip孵育1小时在37 C，ProteoChip洗PBST和蒸馏水，在氮气下干燥。下一步，化合物被溶解100% DMSO稀释至所需浓度在10毫米octyl-b-d-glucopyranoside，氯化钙1毫米，1毫米氯化镁，30%甘油PBS。稀释后的化合物和OPN进一步稀释到100毫米10毫米1毫米octyl-b-d-glucopyranoside，CaCl2、MgCl2 1毫米，和30%甘油PBS和斑点上整合素avb3阵列的ProteoChip。抑制剂浓度
正在翻譯中..
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