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bioRxiv · 10.1101/2020.06.30.179549

Proteus software for physics-based protein design

Mignon, D.·Druart, K.·Opuu, V.·Polydorides, S.·Villa, F.·Gaillard, T.·Michael, E.·Archontis, G.·Simonson, T.
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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.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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Mignon, D., Druart, K., Opuu, V., Polydorides, S., Villa, F., Gaillard, T., Michael, E., Archontis, G., Simonson, T.. 2020-07-01. Proteus software for physics-based protein design. https://doi.org/10.1101/2020.06.30.179549

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