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Design of selective and multi‐specific protein‐protein interfaces
Author(s) -
Kortemme Tanja
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.407.1
Subject(s) - protein design , representation (politics) , sequence (biology) , computer science , sequence space , protein–protein interaction , function (biology) , protein function , protein engineering , computational biology , protein structure , biological system , chemistry , biology , mathematics , genetics , biochemistry , banach space , politics , political science , gene , pure mathematics , law , enzyme
We develop and apply computational models towards the ultimate goal to delineate and quantitatively characterize sets of protein‐protein interactions controlling complex biological processes. This talk will focus on computational protein design approaches to modulate interactions formed by “hubs” in interaction networks and to “simplify” sets of interactions by engineering new protein pairs with altered specificity and reduced cross‐reactivity. I will also describe recent progress towards improving our protein design models in two respects, (1) to more accurately model changes in protein conformation in response to sequence perturbations predicted by design simulations, and (2), to optimize protein sequences for multiple fitness criteria, such as to adopt multiple conformations or to function within a network of proteins where correct interactions should be favored and unwanted interactions avoided. Combining a representation of proteins as conformational ensembles with sequence design shows encouraging results for predicting tolerated sequence space for a given fold or interaction, and makes testable predictions for altering patterns of interactions within sets of interaction proteins.