CNRS - AIX MARSEILLE UNIV: UMR7257


Our laboratory


The Architecture et Fonction des Macromolécules Biologiques (AFMB) laboratory, overseen by the CNRS and AMU, is a center of structural biology localized on the Luminy campus in the South of Marseilles, France, and in partnership with INRA under contract. The aim of our researches is to depict the architecture of proteins or macromolecular assemblies at the molecular level to understand the biological mechanisms which they govern. The description of interactions between macromolecules or a macromolecule and a ligand is also crucial to manipulate these complex molecules. Finally, to understand the molecular diversity of members of some protein families, we also analyze the big data issued from large-scale genome sequencing centers.


Seminars
  • Monday May 14 at 11am: Sarel Fleishman, Weizmann Institute of Science, Dept. Biomolecular Sciences, Rehovot, Israel (amphi CIML). "Computational design of antibodies, enzymes and vaccine immunogens"

    Abstract (...)

    Abstract Computational​ ​protein​ ​design​ ​is​ ​making​ ​substantial​ ​progress,​ ​and​ ​has​ ​generated​ ​stable​ ​and accurate​ ​small​ ​protein​ ​folds,​ ​coiled​ ​coils,​ ​and​ ​large​ ​oligomeric​ ​assemblies.​ ​The​ ​design​ ​of​ ​protein binders​ ​and​ ​enzymes,​ ​by​ ​contrast,​ ​has​ ​been​ ​less​ ​successful,​ ​mainly​ ​due​ ​to​ ​the​ ​large​ ​size​ ​and complexity​ ​of​ ​most​ ​functional​ ​proteins.​ ​To​ ​address​ ​the​ ​challenge​ ​of​ ​designing​ ​functional​ ​proteins, we​ ​have​ ​developed​ ​a​ ​strategy​ ​that​ ​uses​ ​evolutionary​ ​principles​ ​to​ ​guide​ ​atomistic​ ​design calculations​ ​in​ ​the​ ​Rosetta​ ​software​ ​suite​ ​for​ ​biomolecular​ ​design.​ ​Using​ ​this​ ​strategy,​ ​we developed​ ​the​ ​PROSS​ ​algorithm​ ​and​ ​webserver​ ​for​ ​fully​ ​automated​ ​protein​ ​stability​ ​design;​ ​for instance,​ ​we​ ​designed​ ​the​ ​first​ ​variants​ ​of​ ​the​ ​human​ ​enzyme​ ​acetylcholinesterase​ ​that​ ​are expressible,​ ​stable​ ​and​ ​fully​ ​functional​ ​in​ ​bacterial​ ​cells.​ ​We​ ​extended​ ​the​ ​method​ ​to​ ​the​ ​design​ ​of challenging​ ​microbial​ ​proteins​ ​that​ ​may​ ​serve​ ​as​ ​vaccine​ ​immunogens,​ ​and​ ​applied​ ​it​ ​to​ ​designing a​ ​variant​ ​of​ ​the​ ​malaria​ ​parasite​ ​protein​ ​RH5​ ​that​ ​can​ ​be​ ​produced​ ​economically​ ​in​ ​bacterial​ ​cells and​ ​is​ ​stable​ ​in​ ​the​ ​elevated​ ​temperatures​ ​typical​ ​of​ ​sub-Saharan​ ​Africa,​ ​where​ ​malaria​ ​is prevalent.​ ​This​ ​strategy​ ​can​ ​also​ ​be​ ​used​ ​to​ ​design​ ​variants​ ​of​ ​antibodies​ ​and​ ​enzymes​ ​with 100-1,000​ ​fold​ ​improved​ ​affinity​ ​or​ ​catalytic​ ​rate.​ ​We​ ​also​ ​extended​ ​this​ ​strategy​ ​to​ ​designing​ ​new antibodies​ ​and​ ​enzymes​ ​based​ ​on​ ​backbone​ ​conformations​ ​and​ ​sequence-conservation​ ​data​ ​from natural​ ​ones.​ ​This​ ​method,​ ​called​ ​AbDesign,​ ​has​ ​generated​ ​new​ ​binders​ ​and​ ​enzymes​ ​with​ ​high stability,​ ​specificity,​ ​activity,​ ​and​ ​accuracy.​ ​The​ ​design​ ​methods​ ​are​ ​fully​ ​automated,​ ​and​ ​will enable​ ​the​ ​complete​ ​computational​ ​design​ ​of​ ​antibodies​ ​or​ ​enzymes​ ​with​ ​desired​ ​molecular properties.
    All seminars
News
  • This February, INSB highlights the work of Philippe Leone and co-workers on the type IX secretion system
    See here
  • The AFMB lab, via Isabelle Imbert and François Ferron, spotlighted by the INSB dept of the CNRS in December
    See here
Events
  • The AFMB lab contributed again to the Fête de la Science in October 2017
    See here



AFMB - UMR7257 CNRS - Aix-Marseille Univ. - Case 932
163 Avenue de Luminy 13288 Marseille CEDEX 09 FRANCE


Latest Publications

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