Protein-protein recognition and interaction hot spots in an antigen-antibody complex: Free energy decomposition identifies 'efficient amino acids'
| Autor: | Virginie Lafont, Danièle Altschuh, Michael Schaefer, Annick Dejaegere, Roland H. Stote |
|---|---|
| Přispěvatelé: | Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular MESH: Egg Proteins Antigen-Antibody Complex MESH: Amino Acids Static Electricity Binding energy Immunoglobulin Variable Region MESH: Immunoglobulin Variable Region 010402 general chemistry 01 natural sciences Biochemistry 03 medical and health sciences chemistry.chemical_compound Molecular dynamics MESH: Electrostatics Structural Biology Animals MESH: Protein Binding MESH: Animals Amino Acids Molecular Biology 030304 developmental biology chemistry.chemical_classification 0303 health sciences Binding Sites Egg Proteins fungi MESH: Chickens Rational design [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology MESH: Antigen-Antibody Complex Protein engineering Small molecule 0104 chemical sciences Amino acid MESH: Binding Sites chemistry MESH: Muramidase MESH: Camelids New World Thermodynamics Muramidase MESH: Thermodynamics Lysozyme Camelids New World Chickens MESH: Models Molecular Protein Binding |
| Zdroj: | Proteins-Structure, Function and Bioinformatics Proteins-Structure, Function and Bioinformatics, Wiley, 2007, 67 (2), pp.418-34. ⟨10.1002/prot.21259⟩ |
| ISSN: | 0887-3585 1097-0134 |
| DOI: | 10.1002/prot.21259 |
| Popis: | The molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) method was applied to the study of the protein–protein complex between a camelid single chain variable domain (cAb-Lys3) and hen egg white lysozyme (HEL), and between cAb-Lys3 and turkey egg white lysozyme (TEL). The electrostatic energy was estimated by solving the linear Poisson–Boltzmann equation. A free energy decomposition scheme was developed to determine binding energy hot spots of each complex. The calculations identified amino acids of the antibody that make important contributions to the interaction with lysozyme. They further showed the influence of small structural variations on the energetics of binding and they showed that the antibody amino acids that make up the hot spots are organized in such a way as to mimic the lysozyme substrate. Through further analysis of the results, we define the concept of “efficient amino acids,” which can provide an assessment of the binding potential of a particular hot spot interaction. This information, in turn, can be useful in the rational design of small molecules that mimic the antibody. The implications of using free energy decomposition to identify regions of a protein–protein complex that could be targeted by small molecules inhibitors are discussed. Proteins 2007. © 2007 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text