Protein engineering by combined computational and in vitro evolution approaches

L Rosenfeld, M Heyne, JM Shifman, N Papo - Trends in biochemical …, 2016 - cell.com
Two alternative strategies are commonly used to study protein–protein interactions (PPIs)
and to engineer protein-based inhibitors. In one approach, binders are selected …

Production and purification of therapeutic enzymes

MÂ Taipa, P Fernandes, CCCR de Carvalho - … Enzymes: Function and …, 2019 - Springer
The use of therapeutic enzymes embraces currently a vast array of applications, abridging
from diggestive disorders to cancer therapy, cardiovascular and lysosomal storage …

Development of high affinity and high specificity inhibitors of matrix metalloproteinase 14 through computational design and directed evolution

V Arkadash, G Yosef, J Shirian, I Cohen… - Journal of Biological …, 2017 - ASBMB
Degradation of the extracellular matrices in the human body is controlled by matrix
metalloproteinases (MMPs), a family of more than 20 homologous enzymes. Imbalance in …

Converting a broad matrix metalloproteinase family inhibitor into a specific inhibitor of MMP‐9 and MMP‐14

J Shirian, V Arkadash, I Cohen, T Sapir… - FEBS …, 2018 - Wiley Online Library
MMP‐14 and MMP‐9 are two well‐established cancer targets for which no specific clinically
relevant inhibitor is available. Using a powerful combination of computational design and …

Saturation scanning of ubiquitin variants reveals a common hot spot for binding to USP2 and USP21

I Leung, A Dekel, JM Shifman… - Proceedings of the …, 2016 - National Acad Sciences
A detailed understanding of the molecular mechanisms whereby ubiquitin (Ub) recognizes
enzymes in the Ub proteasome system is crucial for understanding the biological function of …

Affinity-and specificity-enhancing mutations are frequent in multispecific interactions between TIMP2 and MMPs

O Sharabi, J Shirian, M Grossman, M Lebendiker… - PloS one, 2014 - journals.plos.org
Multispecific proteins play a major role in controlling various functions such as signaling,
regulation of transcription/translation, and immune response. Hence, a thorough …

Optimizing the specificity window of biomolecular receptors using structure-switching and allostery

S Bissonnette, E Del Grosso, AJ Simon, KW Plaxco… - ACS …, 2020 - ACS Publications
To ensure maximum specificity (ie, minimize cross-reactivity with structurally similar
analogues of the desired target), most bioassays invoke “stringency”, the careful tuning of …

Generating quantitative binding landscapes through fractional binding selections combined with deep sequencing and data normalization

M Heyne, N Papo, JM Shifman - Nature Communications, 2020 - nature.com
Quantifying the effects of various mutations on binding free energy is crucial for
understanding the evolution of protein-protein interactions and would greatly facilitate …

Cold spots in protein binding

J Shirian, O Sharabi, JM Shifman - Trends in biochemical sciences, 2016 - cell.com
Understanding the energetics and architecture of protein-binding interfaces is important for
basic research and could potentially facilitate the design of novel binding domains for …

Combinatorial and computational approaches to identify interactions of macrophage colony-stimulating factor (M-CSF) and its receptor c-FMS

L Rosenfeld, J Shirian, Y Zur, N Levaot… - Journal of Biological …, 2015 - ASBMB
The molecular interactions between macrophage colony-stimulating factor (M-CSF) and the
tyrosine kinase receptor c-FMS play a key role in the immune response, bone metabolism …