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发表于 2010-4-21 02:35:26
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你们都好快啊~
David Baker 4月19日
Experiments this past week have made us even more confident that the designed influenza binder is working as in the design model. we used "directed evolution" methods to identify amino acid changes that make the rosetta@home designed protein bind even more tightly to the virus. we found mutations at two positions: first, at an alanine residue in the design, the evolution process found a valine, and inspection of the design model showed some extra space around the alanine that would be filled by the slightly larger valine. the second amino acid change involved a charged aspartate residue in the design that in retrospect was too close to the virus protein--it was changed to a non charged residue which is less energetically costly to bury upon binding.
we are now combining these two substitutions, and expect that the combination should bind still more tightly to the virus than any protein we have tested so far. we should know later this week--I'll keep you posted!
通过上周的实验,我们更加确信我们设计的流感病毒抑制剂正在按照预定的模型起作用.我们通过"定向进化"策略来改造通过Rosetta@Home设计的蛋白质,希望它们能够更紧密地与病毒结合.我们发现两个位点上的突变对结合有利:首先,原先设计中的一个丙氨酸残基,如果突变成缬氨酸会更好,因为分析显示病毒受体在这个丙氨酸周围有更大的空间,而缬氨酸体积较丙氨酸大;另外原先设计中一个带电的天冬氨酸残基,被发现离病毒受体太近了，因此我们把它替换成了中性氨基酸，让它不容易与受体发生碰撞．
我们正在试验这两种突变，希望新抑制剂能够与病毒蛋白结合的更加紧密．这周就能知道结果了－我会贴出来的． |
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发表于 2010-4-21 14:19:20
