Proteus software for physics-based protein design
Proteus software for physics-based protein design
Abstract We describe methods and software for physics-based protein design. The folded state energy combines molecular mechanics with Generalized Born solvent. Sequence and conformation space are sampled with Replica Exchange Monte Carlo, assuming one or a few fixed protein backbone structures and discrete side chain rotamers. Whole protein design and enzyme design are presented as illustrations. Full redesign of three PDZ domains was done using a simple, empirical, unfolded state model. Designed sequences were very similar to natural ones. Enzyme redesign exploited a powerful, adaptive, importance sampling approach that allows the design to directly target substrate binding, reaction rate, catalytic efficiency, or the specificity of these properties. Redesign of tyrosyl-tRNA synthetase stereospecificity is reported as an example.
Mignon David、Druart Karen、Villa Francesco、Opuu Vaitea、Gaillard Thomas、Simonson Thomas、Archontis Georgios、Polydorides Savvas、Michael Eleni
Laboratoire de Biologie Structurale de la Cellule (CNRS UMR7654), Ecole Polytechnique, Institut Polytechnique de ParisLaboratoire de Biologie Structurale de la Cellule (CNRS UMR7654), Ecole Polytechnique, Institut Polytechnique de ParisLaboratoire de Biologie Structurale de la Cellule (CNRS UMR7654), Ecole Polytechnique, Institut Polytechnique de ParisLaboratoire de Biologie Structurale de la Cellule (CNRS UMR7654), Ecole Polytechnique, Institut Polytechnique de ParisLaboratoire de Biologie Structurale de la Cellule (CNRS UMR7654), Ecole Polytechnique, Institut Polytechnique de ParisLaboratoire de Biologie Structurale de la Cellule (CNRS UMR7654), Ecole Polytechnique, Institut Polytechnique de ParisDept. of Physics, University of CyprusDept. of Physics, University of CyprusDept. of Physics, University of Cyprus
生物科学研究方法、生物科学研究技术生物物理学分子生物学
molecular mechanicsimplicit solventMonte Carlo simulationbinding free energymolecular evolution
Mignon David,Druart Karen,Villa Francesco,Opuu Vaitea,Gaillard Thomas,Simonson Thomas,Archontis Georgios,Polydorides Savvas,Michael Eleni.Proteus software for physics-based protein design[EB/OL].(2025-03-28)[2025-05-17].https://www.biorxiv.org/content/10.1101/2020.06.30.179549.点此复制
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