Journal ArticleDOI
Principles of Protein Stability and Their Application in Computational Design
TLDR
The computational stability design methods have advanced over the past two decades starting from methods that selectively addressed only some aspects of marginal stability, such as thermodynamic, cellular, and evolutionary principles and mechanisms that underlie marginal stability as mentioned in this paper.Abstract:
Proteins are increasingly used in basic and applied biomedical research.Many proteins, however, are only marginally stable and can be expressed in limited amounts, thus hampering research and applications. Research has revealed the thermodynamic, cellular, and evolutionary principles and mechanisms that underlie marginal stability. With this growing understanding, computational stability design methods have advanced over the past two decades starting from methods that selectively addressed only some aspects of marginal stability. Current methods are more general and, by combining phylogenetic analysis with atomistic design, have shown drastic improvements in solubility, thermal stability, and aggregation resistance while maintaining the protein’s primary molecular activity. Stability design is opening the way to rational engineering of improved enzymes, therapeutics, and vaccines and to the application of protein design methodology to large proteins and molecular activities that have proven challenging in...read more
Citations
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Advances in protein structure prediction and design
Brian Kuhlman,Philip Bradley +1 more
TL;DR: Improvements in computational algorithms and technological advances have dramatically increased the accuracy and speed of protein structure modelling, providing novel opportunities for controlling protein function, with potential applications in biomedicine, industry and research.
Posted Content
Funnels, Pathways and the Energy Landscape of Protein Folding: A Synthesis
TL;DR: In this paper, the authors use the energy landscape approach to understand the structure of protein foldings and the mechanism of protein folding, and the success of energy landscape ideas in protein structure prediction.
Journal ArticleDOI
Automated Design of Efficient and Functionally Diverse Enzyme Repertoires
Olga Khersonsky,Rosalie Lipsh,Ziv Avizemer,Yacov Ashani,Moshe Goldsmith,Haim Leader,Orly Dym,Shelly Rogotner,Devin L. Trudeau,Jaime Prilusky,Pep Amengual-Rigo,Victor Guallar,Dan S. Tawfik,Sarel J. Fleishman +13 more
TL;DR: FuncLib, an automated method for designing multipoint mutations at enzyme active sites using phylogenetic analysis and Rosetta design calculations, is described and opened the way to designing highly efficient and diverse catalytic repertoires.
Journal ArticleDOI
Protein stability engineering insights revealed by domain-wide comprehensive mutagenesis
TL;DR: An automated method to generate thermodynamic stability data for nearly every single mutant in a small 56-residue protein is developed and reveals that most single mutants have a neutral effect on stability, mutational sensitivity is largely governed by residue burial, and unexpectedly, hydrophobics are the best tolerated amino acid type.
Journal ArticleDOI
Synthetic Biochemistry: The Bio-inspired Cell-Free Approach to Commodity Chemical Production.
James U. Bowie,Saken Sherkhanov,Tyler P. Korman,Meaghan Valliere,Paul H. Opgenorth,Hongjiang Liu +5 more
TL;DR: The field of designing and implementing reliable and efficient enzyme systems that replace cellular metabolism, synthetic biochemistry is called.
References
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Journal ArticleDOI
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