ArticlePloS one2014
Redistribution of flexibility in stabilizing antibody fragment mutants follows Le Châtelier's principle.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Spectroscopic analysis of the bacterially expressed head domain of rotavirus VP6.Bioscience reports · 2024Article
- Protein Function Analysis through Machine Learning.Biomolecules · 2022Review
- Fewer Dimensions, More Structures for Improved Discrete Models of Dynamics of Free versus Antigen-Bound Antibody.Biomolecules · 2022Article
- Communication pathways bridge local and global conformations in an IgG4 antibody.Scientific reports · 2021Article
- The Allosteric Effect in Antibody-Antigen Recognition.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Rigidity and flexibility characteristics of DD[E/D]-transposases Mos1 and Sleeping Beauty.Proteins · 2019Article
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- In Silico Methods in Antibody Design.Antibodies (Basel, Switzerland) · 2018Review
- Local and global anatomy of antibody-protein antigen recognition.Journal of molecular recognition : JMR · 2018Article
- Repertoire Analysis of Antibody CDR-H3 Loops Suggests Affinity Maturation Does Not Typically Result in Rigidification.Frontiers in immunology · 2018Article
- Decomposing Dynamical Couplings in Mutated scFv Antibody Fragments into Stabilizing and Destabilizing Effects.Journal of the American Chemical Society · 2017Article
- Mechanisms of recognition of amyloid-β (Aβ) monomer, oligomer, and fibril by homologous antibodies.The Journal of biological chemistry · 2017Article
- JED: a Java Essential Dynamics Program for comparative analysis of protein trajectories.BMC bioinformatics · 2017Article
- Alanine 501 Mutations in Penicillin-Binding Protein 2 from Neisseria gonorrhoeae: Structure, Mechanism, and Effects on Cephalosporin Resistance and Biological Fitness.Biochemistry · 2017Article
- Comparative Study of the Collective Dynamics of Proteins and Inorganic Nanoparticles.Scientific reports · 2017Article
- Allosteric control of antibody-prion recognition through oxidation of a disulfide bond between the CH and CL chains.Protein engineering, design & selection : PEDS · 2017Article
- Mutations in Antibody Fragments Modulate Allosteric Response Via Hydrogen-Bond Network Fluctuations.Biophysical journal · 2016Article
- Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Rigid Residue Scan Simulations Systematically Reveal Residue Entropic Roles in Protein Allostery.PLoS computational biology · 2016Article
- Application of Rigidity Theory to the Thermostabilization of Lipase A from Bacillus subtilis.PLoS computational biology · 2016Article
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6 authors.
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Abstract
Le Châtelier's principle is the cornerstone of our understanding of chemical equilibria. When a system at equilibrium undergoes a change in concentration or thermodynamic state (i.e., temperature, pressure, etc.), La Châtelier's principle states that an equilibrium shift will occur to offset the perturbation and a new equilibrium is established. We demonstrate that the effects of stabilizing mutations on the rigidity ⇔ flexibility equilibrium within the native state ensemble manifest themselves through enthalpy-entropy compensation as the protein structure adjusts to restore the global balance between the two. Specifically, we characterize the effects of mutation to single chain fragments of the anti-lymphotoxin-β receptor antibody using a computational Distance Constraint Model. Statistically significant changes in the distribution of both rigidity and flexibility within the molecular structure is typically observed, where the local perturbations often lead to distal shifts in flexibility and rigidity profiles. Nevertheless, the net gain or loss in flexibility of individual mutants can be skewed. Despite all mutants being exclusively stabilizing in this dataset, increased flexibility is slightly more common than increased rigidity. Mechanistically the redistribution of flexibility is largely controlled by changes in the H-bond network. For example, a stabilizing mutation can induce an increase in rigidity locally due to the formation of new H-bonds, and simultaneously break H-bonds elsewhere leading to increased flexibility distant from the mutation site via Le Châtelier. Increased flexibility within the VH β4/β5 loop is a noteworthy illustration of this long-range effect.
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