A. Ramanathan, A. Savol, V. Burger, C. S. Chennubhotla, and P. K. Agarwal, Protein conformational populations and functionally relevant substates, Acc Chem Res, vol.47, pp.149-156, 2014.

K. Henzler-wildman and D. Kern, Dynamic personalities of proteins, Nature, vol.450, pp.964-972, 2007.

G. Bhabha, A dynamic knockout reveals that conformational fluctuations influence the chemical step of enzyme catalysis, Science, vol.332, pp.234-238, 2011.

D. D. Boehr, D. Mcelheny, H. J. Dyson, and P. E. Wright, Millisecond timescale fluctuations in dihydrofolate reductase are exquisitely sensitive to the bound ligands, Proc Natl Acad Sci, vol.107, pp.1373-1378, 2010.

D. Gagné, Perturbation of the Conformational Dynamics of an Active-Site Loop Alters Enzyme Activity, Structure, vol.23, pp.2256-2266, 2015.

E. Z. Eisenmesser, Intrinsic dynamics of an enzyme underlies catalysis, Nature, vol.438, pp.117-121, 2005.

J. P. Klinman, Dynamically Achieved Active Site Precision in Enzyme Catalysis, Accounts of Chemical Research, vol.48, pp.449-456, 2015.

A. C. Gibbs, Elements and modulation of functional dynamics, J Med Chem, vol.57, pp.7819-7837, 2014.

L. C. James and D. S. Tawfik, Conformational diversity and protein evolution -a 60-year-old hypothesis revisited, Trends in Biochemical Sciences, vol.28, pp.361-368, 2003.

M. Morange, What history tells us XLII. A 'new' view of proteins, Journal of Biosciences, vol.42, pp.11-14, 2017.

M. A. Maria-solano, E. Serrano-hervás, A. Romero-rivera, J. Iglesias-fernández, and S. Osuna, Role of conformational dynamics in the evolution of novel enzyme function, Chemical Communications, vol.54, pp.6622-6634, 2018.

O. Keskin, R. L. Jernigan, and I. Bahar, Proteins with similar architecture exhibit similar large-scale dynamic behavior, Biophys J, vol.78, pp.76756-76763, 2000.

S. Maguid, S. Fernandez-alberti, and J. Echave, Evolutionary conservation of protein vibrational dynamics, Gene, vol.422, pp.7-13, 2008.

A. Ramanathan and P. K. Agarwal, Evolutionarily conserved linkage between enzyme fold, flexibility, and catalysis, PLoS Biol, vol.9, 2011.

K. Francis, V. Stojkovic, and A. Kohen, Preservation of protein dynamics in dihydrofolate reductase evolution, J Biol Chem, vol.288, pp.35961-35968, 2013.

D. Gagné, L. A. Charest, S. Morin, E. L. Kovrigin, and N. Doucet, Conservation of flexible residue clusters among structural and functional enzyme homologues, J Biol Chem, vol.287, pp.44289-44300, 2012.

S. M. Gobeil, Maintenance of Native-like Protein Dynamics May Not Be Required for Engineering Functional Proteins, Chemistry & biology, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01196413

Y. Liu and I. Bahar, Sequence evolution correlates with structural dynamics, Mol Biol Evol, vol.29, pp.2253-2263, 2012.

C. Narayanan, Conservation of Dynamics Associated with Biological Function in an Enzyme Superfamily, Structure, vol.26, pp.426-436, 2018.
URL : https://hal.archives-ouvertes.fr/pasteur-01856081

G. Bhabha, Divergent evolution of protein conformational dynamics in dihydrofolate reductase, Nat Struct Mol Biol, vol.20, pp.1243-1249, 2013.

N. Tokuriki and D. S. Tawfik, Protein dynamism and evolvability, Science, vol.324, pp.203-207, 2009.

E. Campbell, The role of protein dynamics in the evolution of new enzyme function, Nature Chemical Biology, 2016.

E. C. Campbell, Laboratory evolution of protein conformational dynamics, Current Opinion in Structural Biology, vol.50, pp.49-57, 2018.

R. Otten, Rescue of conformational dynamics in enzyme catalysis by directed evolution, Nature Communications, vol.9, 2018.

C. A. Voigt, C. Martinez, Z. G. Wang, S. L. Mayo, and F. H. Arnold, Protein building blocks preserved by recombination, Nat Struct Biol, vol.9, pp.553-558, 2002.

S. O. Meroueh, Molecular dynamics at the root of expansion of function in the M69L inhibitor-resistant TEM beta-lactamase from Escherichia coli, J Am Chem Soc, vol.124, pp.9422-9430, 2002.

S. Morin and S. M. Gagné, NMR dynamics of PSE-4 beta-lactamase: an interplay of ps-ns order and mus-ms motions in the active site, Biophys J, vol.96, pp.4681-4691, 2009.

P. Y. Savard and S. M. Gagné, Backbone dynamics of TEM-1 determined by NMR: evidence for a highly ordered protein, Biochemistry, vol.45, pp.11414-11424, 2006.

C. M. Clouthier, Chimeric beta-lactamases: global conservation of parental function and fast time-scale dynamics with increased slow motions, PloS one, vol.7, 2012.

D. Lim, Insights into the molecular basis for the carbenicillinase activity of PSE-4 beta-lactamase from crystallographic and kinetic studies, Biochemistry, vol.40, pp.395-402, 2001.

E. Fonze, TEM1 beta-lactamase structure solved by molecular replacement and refined structure of the S235A mutant, Acta Crystallogr D Biol Crystallogr, vol.51, pp.682-694, 1995.

M. M. Meyer, L. Hochrein, and F. H. Arnold, Structure-guided SCHEMA recombination of distantly related beta-lactamases, Protein Eng Des Sel, vol.19, pp.563-570, 2006.

Z. Yuan, T. L. Bailey, and R. D. Teasdale, Prediction of protein B-factor profiles, Proteins: Structure, Function, and Bioinformatics, vol.58, pp.905-912, 2005.

E. Dellus-gur, A. Toth-petroczy, M. Elias, and D. S. Tawfik, What Makes a Protein Fold Amenable to Functional Innovation? Fold Polarity and Stability Trade-offs, Journal of Molecular Biology, vol.425, pp.2609-2621, 2013.

O. Carugo, How large B-factors can be in protein crystal structures, BMC Bioinformatics, vol.19, 2018.

A. Kuzmanic, N. S. Pannu, and B. Zagrovic, X-ray refinement significantly underestimates the level of microscopic heterogeneity in biomolecular crystals, Nature Communications, vol.5, 2014.

D. Choury, Nucleotide Sequence of the blaRTG-2 (CARB-5) Gene and Phylogeny of a New Group of Carbenicillinases, Antimicrobial Agents and Chemotherapy, vol.44, pp.1070-1074, 2000.

G. Minasov, X. Wang, and B. K. Shoichet, An ultrahigh resolution structure of TEM-1 beta-lactamase suggests a role for Glu166 as the general base in acylation, J Am Chem Soc, vol.124, pp.5333-5340, 2002.

C. Zeil, M. Widmann, S. Fademrecht, C. Vogel, and J. Pleiss, Network Analysis of Sequence-Function Relationships and Exploration of Sequence Space of TEM ?-Lactamases, Antimicrobial Agents and Chemotherapy, vol.60, pp.2709-2717, 2016.

S. M. Gobeil, D. Gagné, N. Doucet, and J. N. Pelletier, backbone resonance assignments of an artificially engineered TEM-1/PSE-4 class A beta-lactamase chimera and its deconvoluted mutant, Biomol NMR Assign, 2015.

B. Stec, K. M. Holtz, C. L. Wojciechowski, and E. R. Kantrowitz, Structure of the wild-type TEM-1 beta-lactamase at 1.55 A and the mutant enzyme Ser70Ala at 2.1 A suggest the mode of noncovalent catalysis for the mutant enzyme, Acta Crystallogr D Biol Crystallogr, vol.61, pp.1072-1079, 2005.

S. C. Lovell, J. M. Word, J. S. Richardson, and D. C. Richardson, The penultimate rotamer library, Proteins, vol.40, pp.389-408, 2000.

N. Doucet and J. N. Pelletier, Simulated annealing exploration of an active-site tyrosine in TEM-1 beta-lactamase suggests the existence of alternate conformations, Proteins, vol.69, pp.340-348, 2007.
URL : https://hal.archives-ouvertes.fr/pasteur-00736957

H. Christensen, M. T. Martin, and S. G. Waley, Beta-lactamases as fully efficient enzymes. Determination of all the rate constants in the acyl-enzyme mechanism, Biochem J, vol.266, pp.853-861, 1990.

M. G. Page, Extended-spectrum ?-lactamases: structure and kinetic mechanism, Clinical Microbiology and Infection, vol.14, pp.63-74, 2008.

S. Morin, C. M. Clouthier, S. Gobeil, J. N. Pelletier, and S. M. Gagné, Backbone resonance assignments of an artificially engineered TEM-1/PSE-4 Class A beta-lactamase chimera, Biomol NMR Assign, vol.4, pp.127-130, 2010.

P. Y. Savard, A. Sosa-peinado, R. C. Levesque, M. W. Makinen, S. M. Gagné et al., 13C and 15N backbone resonance assignments for TEM-1, a 28.9 kDa beta-lactamase from E. coli, Journal of biomolecular NMR, vol.29, pp.433-434, 2004.

S. Morin, R. C. Levesque, and S. M. Gagné, 1H, 13C, and 15N backbone resonance assignments for PSE-4, a 29.5 kDa class A betalactamase from Pseudomonas aeruginosa, Journal of biomolecular NMR, vol.36, issue.1, 2006.

D. Marion, An introduction to biological NMR spectroscopy, Mol Cell Proteomics, vol.12, pp.3006-3025, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01321578

A. K. Mittermaier and L. E. Kay, Observing biological dynamics at atomic resolution using NMR, Trends Biochem Sci, vol.34, pp.601-611, 2009.

I. R. Kleckner and M. P. Foster, An introduction to NMR-based approaches for measuring protein dynamics, Biochim Biophys Acta, vol.1814, pp.942-968, 2011.

N. Díaz, T. L. Sordo, K. M. Merz, and D. Suárez, Insights into the Acylation Mechanism of Class A ?-Lactamases from Molecular Dynamics Simulations of the TEM-1 Enzyme Complexed with Benzylpenicillin, Journal of the American Chemical Society, vol.125, pp.672-684, 2003.

N. Doucet, P. Y. De-wals, and J. N. Pelletier, Site-saturation mutagenesis of Tyr-105 reveals its importance in substrate stabilization and discrimination in TEM-1 beta-lactamase, J Biol Chem, vol.279, pp.46295-46303, 2004.
URL : https://hal.archives-ouvertes.fr/pasteur-00736939

O. F. Lange, Recognition Dynamics Up to Microseconds Revealed from an RDC-Derived Ubiquitin Ensemble in Solution, Science, vol.320, pp.1471-1475, 2008.

Z. Sun, Q. Liu, G. Qu, Y. Feng, and M. T. Reetz, Utility of B-Factors in Protein Science: Interpreting Rigidity, Flexibility, and Internal Motion and Engineering Thermostability, Chemical Reviews, vol.119, pp.1626-1665, 2019.

R. B. Fenwick, H. Van-den-bedem, J. S. Fraser, and P. E. Wright, Integrated description of protein dynamics from room-temperature X-ray crystallography and NMR, Proceedings of the National Academy of Sciences, vol.111, pp.445-454, 2014.

V. Agarwal, Y. Xue, B. Reif, and N. R. Skrynnikov, Protein Side-Chain Dynamics As Observed by Solution-and Solid-State NMR Spectroscopy: A Similarity Revealed, Journal of the American Chemical Society, vol.130, pp.16611-16621, 2008.

J. Yang, M. L. Tasayco, and T. Polenova, Dynamics of Reassembled Thioredoxin Studied by Magic Angle Spinning NMR: Snapshots from Different Time Scales, Journal of the American Chemical Society, vol.131, pp.13690-13702, 2009.

B. Halle, Flexibility and packing in proteins, Proceedings of the National Academy of Sciences, vol.99, pp.1274-1279, 2002.

M. Rueda, A consensus view of protein dynamics, Proceedings of the National Academy of Sciences, vol.104, pp.796-801, 2007.

V. Kurauskas, Slow conformational exchange and overall rocking motion in ubiquitin protein crystals, Nature Communications, vol.8, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01538940

K. Lindorff-larsen, P. Maragakis, S. Piana, and D. E. Shaw, Picosecond to Millisecond Structural Dynamics in Human Ubiquitin, The Journal of Physical Chemistry B, vol.120, pp.8313-8320, 2016.

C. A. Smith, Allosteric switch regulates protein-protein binding through collective motion, Proceedings of the National Academy of Sciences, vol.113, pp.3269-3274, 2016.

C. Schmidt-dannert and F. H. Arnold, Directed evolution of industrial enzymes, Trends in Biotechnology, vol.17, pp.135-136, 1999.

M. M. Gonzalez, L. A. Abriata, P. E. Tomatis, and A. J. Vila, Optimization of Conformational Dynamics in an Epistatic Evolutionary Trajectory, Mol Biol Evol, 2016.

V. A. Risso, De novo active sites for resurrected Precambrian enzymes, Nature. Communications, vol.8, p.16113, 2017.

K. Lindorff-larsen, Improved side-chain torsion potentials for the Amber ff99SB protein force field, Proteins, vol.78, pp.1950-1958, 2010.

M. J. Abraham, GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers, 2015.

, Scientific RepoRts |, vol.9, p.6656, 2019.

G. Lipari and A. Szabo, Model-Free Approach to the Interpretation of Nuclear Magnetic-Resonance Relaxation in Macromolecules .1. Theory and Range of Validity, Journal of the American Chemical Society, vol.104, pp.4546-4559, 1982.

J. P. Loria, M. Rance, and A. G. Palmer, 3rd A TROSY CPMG sequence for characterizing chemical exchange in large proteins, Journal of biomolecular NMR, vol.15, pp.151-155, 1999.

G. Manley and J. P. Loria, NMR insights into protein allostery, Archives of Biochemistry and Biophysics, vol.519, pp.223-231, 2012.

R. P. Ambler, A standard numbering scheme for the class A beta-lactamases, Biochem J, vol.276, pp.269-270, 1991.