Computational design and experimental optimization of protein binders with prospects for biomedical applications

被引:8
作者
Bonadio, Alessandro [1 ]
Shifman, Julia M. [1 ]
机构
[1] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, IL-9190401 Jerusalem, Israel
基金
美国国家卫生研究院; 以色列科学基金会; 美国国家科学基金会;
关键词
affinity reagents; protein binder; protein design; protein engineering; protein-based inhibitors; YEAST SURFACE DISPLAY; DE-NOVO DESIGN; HIGH-AFFINITY; SCAFFOLDS; COMBINATORIAL; SPECIFICITY; INHIBITORS; EVOLUTION; EPITOPE;
D O I
10.1093/protein/gzab020
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
Protein-based binders have become increasingly more attractive candidates for drug and imaging agent development. Such binders could be evolved from a number of different scaffolds, including antibodies, natural protein effectors and unrelated small protein domains of different geometries. While both computational and experimental approaches could be utilized for protein binder engineering, in this review we focus on various computational approaches for protein binder design and demonstrate how experimental selection could be applied to subsequently optimize computationally-designed molecules. Recent studies report a number of designed protein binders with pM affinities and high specificities for their targets. These binders usually characterized with high stability, solubility, and low production cost. Such attractive molecules are bound to become more common in various biotechnological and biomedical applications in the near future.
引用
收藏
页数:7
相关论文
共 64 条
[51]   Affinity- and Specificity-Enhancing Mutations Are Frequent in Multispecific Interactions between TIMP2 and MMPs [J].
Sharabi, Oz ;
Shirian, Jason ;
Grossman, Moran ;
Lebendiker, Mario ;
Sagi, Irit ;
Shifman, Julia .
PLOS ONE, 2014, 9 (04)
[52]   Converting a broad matrix metalloproteinase family inhibitor into a specific inhibitor of MMP-9 and MMP-14 [J].
Shirian, Jason ;
Arkadash, Valeria ;
Cohen, Itay ;
Sapir, Tamila ;
Radisky, Evette S. ;
Papo, Niv ;
Shifman, Julia M. .
FEBS LETTERS, 2018, 592 (07) :1122-1134
[53]   Cold Spots in Protein Binding [J].
Shirian, Jason ;
Sharabi, Oz ;
Shifman, Julia M. .
TRENDS IN BIOCHEMICAL SCIENCES, 2016, 41 (09) :739-745
[54]   De novo design of potent and selective mimics of IL-2 and IL-15 [J].
Silva, Daniel-Adriano ;
Yu, Shawn ;
Ulge, Umut Y. ;
Spangler, Jamie B. ;
Jude, Kevin M. ;
Labao-Almeida, Carlos ;
Ali, Lestat R. ;
Quijano-Rubio, Alfredo ;
Ruterbusch, Mikel ;
Leung, Isabel ;
Biary, Tamara ;
Crowley, Stephanie J. ;
Marcos, Enrique ;
Walkey, Carl D. ;
Weitzner, Brian D. ;
Pardo-Avila, Fatima ;
Castellanos, Javier ;
Carter, Lauren ;
Stewart, Lance ;
Riddell, Stanley R. ;
Pepper, Marion ;
Bernardes, Goncalo J. L. ;
Dougan, Michael ;
Garcia, K. Christopher ;
Baker, David .
NATURE, 2019, 565 (7738) :186-+
[55]   In vitro-engineered non-antibody protein therapeutics [J].
Simeon, Rudo ;
Chen, Zhilei .
PROTEIN & CELL, 2018, 9 (01) :3-14
[56]   Alternative non-antibody scaffolds for molecular recognition [J].
Skerra, Arne .
CURRENT OPINION IN BIOTECHNOLOGY, 2007, 18 (04) :295-304
[57]   Non-immunoglobulin scaffolds: a focus on their targets [J].
Skrlec, Katja ;
Strukelj, Borut ;
Berlec, Ales .
TRENDS IN BIOTECHNOLOGY, 2015, 33 (07) :408-418
[58]   Computational design of a symmetric homodimer using β-strand assembly [J].
Stranges, P. Benjamin ;
Machius, Mischa ;
Miley, Michael J. ;
Tripathy, Ashutosh ;
Kuhlman, Brian .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (51) :20562-20567
[59]   Computational design of a pH-sensitive IgG binding protein [J].
Strauch, Eva-Maria ;
Fleishman, Sarel J. ;
Baker, David .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (02) :675-680
[60]   Challenges and opportunities for non-antibody scaffold drugs [J].
Vazquez-Lombardi, Rodrigo ;
Phan, Tri Giang ;
Zimmermann, Carsten ;
Lowe, David ;
Jermutus, Lutz ;
Christ, Daniel .
DRUG DISCOVERY TODAY, 2015, 20 (10) :1271-1283