Laboratory evolution of protein conformational dynamics.

This review focuses on recent work that has begun to establish specific functional roles for protein conformational dynamics, specifically how the conformational landscapes that proteins can sample can evolve under laboratory based evolutionary selection. We discuss recent technical advances in computational and biophysical chemistry, which have provided us with new ways to dissect evolutionary processes. Finally, we offer some perspectives on the emerging view of conformational dynamics and evolution, and the challenges that we face in rationally engineering conformational dynamics.

[1]  N. Tokuriki,et al.  Enzyme dynamics and engineering: one step at a time. , 2014, Chemistry & biology.

[2]  Jan Brezovsky,et al.  Ancestral Haloalkane Dehalogenases Show Robustness and Unique Substrate Specificity , 2017, Chembiochem : a European journal of chemical biology.

[3]  Dan S. Tawfik,et al.  Conformational sampling, catalysis, and evolution of the bacterial phosphotriesterase , 2009, Proceedings of the National Academy of Sciences.

[4]  C. Cepeda,et al.  Forebrain deletion of the dystonia protein torsinA causes dystonic-like movements and loss of striatal cholinergic neurons , 2015, eLife.

[5]  R. Merkl,et al.  Ancestral protein reconstruction: techniques and applications , 2016, Biological chemistry.

[6]  Fabio Prati,et al.  Negative Epistasis and Evolvability in TEM-1 β-Lactamase--The Thin Line between an Enzyme's Conformational Freedom and Disorder. , 2015, Journal of molecular biology.

[7]  Roberto A Chica,et al.  Multistate approaches in computational protein design , 2012, Protein science : a publication of the Protein Society.

[8]  Guanhua Hou,et al.  Stabilization of different types of transition states in a single enzyme active site: QM/MM analysis of enzymes in the alkaline phosphatase superfamily. , 2013, Journal of the American Chemical Society.

[9]  Marc Garcia-Borràs,et al.  Computational tools for the evaluation of laboratory-engineered biocatalysts , 2016, Chemical communications.

[10]  L. Segovia,et al.  Mimicking natural evolution in metallo-beta-lactamases through second-shell ligand mutations. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[11]  S. Ozkan,et al.  A hinge migration mechanism unlocks the evolution of green-to-red photoconversion in GFP-like proteins. , 2015, Structure.

[12]  Arieh Warshel,et al.  Perspective: Defining and quantifying the role of dynamics in enzyme catalysis. , 2016, The Journal of chemical physics.

[13]  A. Kohen,et al.  Network of remote and local protein dynamics in dihydrofolate reductase catalysis. , 2015, ACS catalysis.

[14]  Lila M Gierasch,et al.  Post-reductionist protein science, or putting Humpty Dumpty back together again. , 2009, Nature chemical biology.

[15]  Christian N. Cunningham,et al.  Conformational dynamics control ubiquitin-deubiquitinase interactions and influence in vivo signaling , 2013, Proceedings of the National Academy of Sciences.

[16]  S. Takada,et al.  Dynamic energy landscape view of coupled binding and protein conformational change: Induced-fit versus population-shift mechanisms , 2008, Proceedings of the National Academy of Sciences.

[17]  K. Lindorff-Larsen,et al.  Picosecond to Millisecond Structural Dynamics in Human Ubiquitin. , 2016, The journal of physical chemistry. B.

[18]  Enrico Guarnera,et al.  Allosteric sites: remote control in regulation of protein activity. , 2016, Current opinion in structural biology.

[19]  Dan S. Tawfik,et al.  Protein Dynamism and Evolvability , 2009, Science.

[20]  David Baker,et al.  Evolution of a designed retro-aldolase leads to complete active site remodeling , 2013, Nature chemical biology.

[21]  Roberto A. Chica,et al.  Iterative approach to computational enzyme design , 2012, Proceedings of the National Academy of Sciences.

[22]  Donald Hilvert,et al.  Precision is essential for efficient catalysis in an evolved Kemp eliminase , 2013, Nature.

[23]  L. Kay,et al.  NMR spectroscopy brings invisible protein states into focus. , 2009, Nature chemical biology.

[24]  R. Kazlauskas,et al.  Improving enzyme properties: when are closer mutations better? , 2005, Trends in biotechnology.

[25]  Arieh Warshel,et al.  Enzyme millisecond conformational dynamics do not catalyze the chemical step , 2009, Proceedings of the National Academy of Sciences.

[26]  J. Fraser,et al.  Integrative, dynamic structural biology at atomic resolution—it's about time , 2015, Nature Methods.

[27]  Steffen Kutter,et al.  Evolutionary drivers of thermoadaptation in enzyme catalysis , 2017, Science.

[28]  Jasmine L. Gallaher,et al.  Computational Design of an Enzyme Catalyst for a Stereoselective Bimolecular Diels-Alder Reaction , 2010, Science.

[29]  David Baker,et al.  Evolutionary optimization of computationally designed enzymes: Kemp eliminases of the KE07 series. , 2010, Journal of molecular biology.

[30]  Jesse B. Hopkins,et al.  Mapping the conformational landscape of a dynamic enzyme by multitemperature and XFEL crystallography , 2015, bioRxiv.

[31]  Adam M Damry,et al.  Prediction of Stable Globular Proteins Using Negative Design with Non-native Backbone Ensembles. , 2015, Structure.

[32]  Liping Yu,et al.  Distinct Roles for Conformational Dynamics in Protein-Ligand Interactions. , 2016, Structure.

[33]  Benjamin T. Porebski,et al.  The role of protein dynamics in the evolution of new enzyme function. , 2016, Nature chemical biology.

[34]  D. Kern,et al.  Hidden alternate structures of proline isomerase essential for catalysis , 2010 .

[35]  David Baker,et al.  Computational design of ligand-binding proteins with high affinity and selectivity , 2013, Nature.

[36]  Dennis M. Krüger,et al.  De novo active sites for resurrected Precambrian enzymes , 2017, Nature Communications.

[37]  T. Kortemme,et al.  A Model for the Molecular Mechanism of an Engineered Light-Driven Protein Machine. , 2016, Structure.

[38]  Nigel S. Scrutton,et al.  Impact of residues remote from the catalytic centre on enzyme catalysis of copper nitrite reductase , 2014, Nature Communications.

[39]  Eric A. Althoff,et al.  De Novo Computational Design of Retro-Aldol Enzymes , 2008, Science.

[40]  David Baker,et al.  Optimization of the in-silico-designed kemp eliminase KE70 by computational design and directed evolution. , 2011, Journal of molecular biology.

[41]  Earl O. P. Solis,et al.  Directed evolution of an ultrastable carbonic anhydrase for highly efficient carbon capture from flue gas , 2014, Proceedings of the National Academy of Sciences.

[42]  Y. Sanejouand,et al.  Semi-rational approach for converting a GH36 α-glycosidase into an α-transglycosidase. , 2015, Glycobiology.

[43]  Christian N. Cunningham,et al.  Flexibility and design: conformational heterogeneity along the evolutionary trajectory of a redesigned ubiquitin , 2016, bioRxiv.

[44]  J Andrew McCammon,et al.  Large conformational changes in proteins: signaling and other functions. , 2010, Current opinion in structural biology.

[45]  Olga Khersonsky,et al.  Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase. , 2005, Biochemistry.

[46]  Colin J Jackson,et al.  Ancestral Protein Reconstruction Yields Insights into Adaptive Evolution of Binding Specificity in Solute-Binding Proteins. , 2016, Cell chemical biology.

[47]  D. Baker,et al.  The coming of age of de novo protein design , 2016, Nature.

[48]  D. Baker,et al.  Emergence of a catalytic tetrad during evolution of a highly active artificial aldolase , 2016, Nature Chemistry.

[49]  Henry van den Bedem,et al.  Integrated description of protein dynamics from room-temperature X-ray crystallography and NMR , 2014, Proceedings of the National Academy of Sciences.

[50]  Justin B Siegel,et al.  Computational enzyme design: transitioning from catalytic proteins to enzymes. , 2014, Current opinion in structural biology.

[51]  M. Drobizhev,et al.  Two-photon directed evolution of green fluorescent proteins , 2015, Scientific Reports.

[52]  Jeroen van den Brink,et al.  The quantum nature of skyrmions and half-skyrmions in Cu2OSeO3 , 2014, Nature Communications.

[53]  Henry van den Bedem,et al.  Exposing Hidden Alternative Backbone Conformations in X-ray Crystallography Using qFit , 2015, bioRxiv.

[54]  Rafael C. Bernardi,et al.  Enhanced sampling techniques in molecular dynamics simulations of biological systems. , 2015, Biochimica et biophysica acta.

[55]  F. Hollfelder,et al.  Reverse evolution leads to genotypic incompatibility despite functional and active site convergence , 2015, eLife.

[56]  R. Nussinov,et al.  The role of dynamic conformational ensembles in biomolecular recognition. , 2009, Nature chemical biology.

[57]  Christopher M. Clouthier,et al.  Maintenance of native-like protein dynamics may not be required for engineering functional proteins. , 2014, Chemistry & biology.

[58]  S. Grzesiek,et al.  Backbone NMR reveals allosteric signal transduction networks in the β1-adrenergic receptor , 2016, Nature.

[59]  Nobuhiko Tokuriki,et al.  How mutational epistasis impairs predictability in protein evolution and design , 2016, Protein science : a publication of the Protein Society.

[60]  Dan S. Tawfik,et al.  Diminishing returns and tradeoffs constrain the laboratory optimization of an enzyme , 2012, Nature Communications.

[61]  F. Arnold,et al.  Directed evolution of cytochrome c for carbon–silicon bond formation: Bringing silicon to life , 2016, Science.

[62]  James A. Davey,et al.  Brighter Red Fluorescent Proteins by Rational Design of Triple-Decker Motif. , 2016, ACS chemical biology.

[63]  Daniel Herschlag,et al.  Robust design and optimization of retroaldol enzymes , 2012, Protein science : a publication of the Protein Society.

[64]  Philip M. Dixon,et al.  Speeding Up Ecological and Evolutionary Computations in R; Essentials of High Performance Computing for Biologists , 2015, PLoS Comput. Biol..

[65]  M. Karplus,et al.  A hierarchy of timescales in protein dynamics is linked to enzyme catalysis , 2007, Nature.

[66]  Eric A. Althoff,et al.  Kemp elimination catalysts by computational enzyme design , 2008, Nature.

[67]  C. Tung,et al.  Dynamic Conformational States Dictate Selectivity toward the Native Substrate in a Substrate-Permissive Acyltransferase. , 2016, Biochemistry.

[68]  Paul D Adams,et al.  Modelling dynamics in protein crystal structures by ensemble refinement , 2012, eLife.

[69]  K N Houk,et al.  Molecular dynamics explorations of active site structure in designed and evolved enzymes. , 2015, Accounts of chemical research.