Title : Mapping of the Binding Landscape for a Picomolar Protein-Protein Complex through Computation and Experiment - Aizner_2014_Structure_22_636 |
Author(s) : Aizner Y , Sharabi O , Shirian J , Dakwar GR , Risman M , Avraham O , Shifman J |
Ref : Structure , 22 :636 , 2014 |
Abstract :
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 Kd, kon, and koff. 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. |
PubMedSearch : Aizner_2014_Structure_22_636 |
PubMedID: 24613488 |
Aizner Y, Sharabi O, Shirian J, Dakwar GR, Risman M, Avraham O, Shifman J (2014)
Mapping of the Binding Landscape for a Picomolar Protein-Protein Complex through Computation and Experiment
Structure
22 :636
Aizner Y, Sharabi O, Shirian J, Dakwar GR, Risman M, Avraham O, Shifman J (2014)
Structure
22 :636