定义和展示空间、疏水性和氢键配体结合位点的蛋白质的性质使用李和理查兹可及表面:验证药物设计的高分辨率的图形工具。

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Bohacek RS, McMartin C

定义和展示空间、疏水性和氢键配体结合位点的蛋白质的性质使用李和理查兹可及表面:验证药物设计的高分辨率的图形工具。

J地中海化学。1992年5月15日,35 (10):1671 - 84。

PubMed ID

1588550 (在PubMed

]

文摘

可及表面,被李和理查兹(L&R表面:j .摩尔。杂志。1971年,55岁,379),有非常有用的属性显示ligand-protein交互。放置一个表面范德华半径+ 1探针原子半径的蛋白质。配体骨架形式显示。与合适的探测半径、配位体的部分范德华接触良好蛋白质结合位点叠加L&R表面。因此显示使用平行的表面轮廓为互动提供了一个非常强大的指导药物设计,因为只有躺在或接近表面的原子配位体在低能接触。表面的能力,准确地显示空间互补性配体和蛋白质之间的优化利用小分子晶体结构数据。显示的可能性的化学特异性结合位点也被调查。表面颜色可以给准确信息化学特异性。静电势、静电梯度和距离氢键组测试显示化学特异性的方法。这些方法来描述互补的能力实际上观察到内部的蛋白质进行了比较。 High-resolution crystal data for ribonuclease and trypsin was used. The environment surrounding extended peptide chains in the protein was treated as a virtual binding site. The peptide chain served as a virtual ligand. This large sample of experimental data was used to measure the correlation between type of ligand atom and the calculated property of the nearest binding site surface. The best correlation was obtained using hydrogen-bonding properties of the binding site. Using this parameter the surface could be divided into three separate zones representing the hydrophobic, hydrogen-bond-acceptor, and hydrogen-bond-donor properties of the binding site. The percentage of hydrophobic ligand atoms found to lie closest to the hydrophobic protein surface was 91%. The equivalent scores for ligand hydrogen-acceptor atoms and hydrogen-donor atoms found at the corresponding complementarity zone were 94% and 91%. The surface zones can be readily displayed using three colors. To test the method on real ligand/binding site interactions, nine thermolysin-inhibitor complexes of known structure were evaluated using the parameters and criteria derived from the protein-packing study and a correlation between complementary contacts and logarithm of potency was obtained which had an r2 of 0.99.(ABSTRACT TRUNCATED AT 400 WORDS)

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绑定属性

药物	目标	财产	测量	pH值	温度(°C)
3 - {((1 r) 1-benzyl-2-sulfanylethyl)氨基}3-oxopropanoic酸	嗜热菌蛋白酶	Ki (nM)	2300年	N /一个	N /一个	细节