共 47 条
Mapping of the Binding Landscape for a Picomolar Protein-Protein Complex through Computation and Experiment
被引:17
作者:
Aizner, Yonatan
[1
]
Sharabi, Oz
[1
]
Shirian, Jason
[1
]
Dakwar, George R.
[1
]
Risman, Marina
[1
]
Avraham, Orly
[1
]
Shifman, Julia
[1
]
机构:
[1] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel
来源:
关键词:
SACCHAROMYCES-CEREVISIAE;
SCANNING MUTAGENESIS;
INTERACTION NETWORK;
CRYSTAL-STRUCTURE;
SNAKE-VENOM;
ACETYLCHOLINESTERASE;
DESIGN;
FASCICULIN;
AFFINITY;
INTERFACE;
D O I:
10.1016/j.str.2014.01.012
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:
Our understanding of protein evolution would greatly benefit from mapping of binding landscapes, i.e., changes in protein-protein binding affinity due to all single mutations. However, experimental generation of such landscapes is a tedious task due to a large number of possible mutations. Here, we use a simple computational protocol to map the binding landscape for two homologous high-affinity complexes, involving a snake toxin fasciculin and acetylcholinesterase from two different species. To verify our computational predictions, we experimentally measure binding between 25 Fas mutants and the 2 enzymes. Both computational and experimental results demonstrate that the Fas sequence is close to the optimum when interacting with its targets, yet a few mutations could further improve K-d, k(on), and k(off). Our computational predictions agree well with experimental results and generate distributions similar to those observed in other high-affinity PPIs, demonstrating the potential of simple computational protocols in capturing realistic binding landscapes.
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页码:636 / 645
页数:10
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