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Protein-protein recognition and interaction hot spots in an antigen-antibody complex: free energy decomposition identifies "efficient amino acids".

Abstract : 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.
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https://hal.archives-ouvertes.fr/hal-00190960
Contributor : Maité Peney Connect in order to contact the contributor
Submitted on : Friday, November 23, 2007 - 12:28:35 PM
Last modification on : Thursday, June 17, 2021 - 3:16:03 PM

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Virginie Lafont, Michael Ke Schaefer, Roland H Stote, Danièle Altschuh, Annick Dejaegere. Protein-protein recognition and interaction hot spots in an antigen-antibody complex: free energy decomposition identifies "efficient amino acids".. Proteins - Structure, Function and Bioinformatics, Wiley, 2007, 67 (2), pp.418-34. ⟨10.1002/prot.21259⟩. ⟨hal-00190960⟩

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