Identification and engineering of highly functional potyviral proteases in cells using co-evolutionary models

To facilitate the testing of thousands of potyviral proteases against peptide targets by multiple laboratories, we created an interactive web application for ProSSpeC (https://coevolutionary.org/prosspec/). Code is available at https://github.com/morcoslab/ProSSpeC and archived on Zenodo with https://doi.org/10.5281/zenodo.18321025³⁵.

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Author notes

1. These authors contributed equally: Medel B. Lim Suan Jr, Cheyenne Ziegler.

Authors and Affiliations

1. Department of Bioengineering, The University of Texas at Dallas, Richardson, TX, USA

   Medel B. Lim Suan Jr, Jaideep Kaur, Faruck Morcos & P. C. Dave P. Dingal

2. Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX, USA

   Cheyenne Ziegler, Zain Syed, Arjun Sai Yedavalli, Jaimahesh Nagineni, Rodrigo Raposo, Ajay Tunikipati, Faruck Morcos & P. C. Dave P. Dingal

3. Center for Systems Biology, The University of Texas at Dallas, Richardson, TX, USA

   Faruck Morcos & P. C. Dave P. Dingal

4. Department of Physics, The University of Texas at Dallas, Richardson, TX, USA

   Faruck Morcos

Contributions

M.B.L., Z.S., A.S.Y., A.T., R.R., J.N., and J.K. performed experiments. M.B.L. and P.C.D.P.D. analyzed experimental results. Computational modeling and full stack development of the ProSSpeC web app performed by C.Z. Conceptual planning and resources provided by P.C.D.P.D. and F.M. M.B.L., C.Z., F.M., and P.C.D.P.D. authored and edited this manuscript, including illustrations. The final version of this manuscript is approved by all authors.

Corresponding authors

Correspondence to Faruck Morcos or P. C. Dave P. Dingal.

Competing interests

The Board of Regents of The University of Texas System have filed a pending patent application on behalf of co-inventors P.C.D.P.D., F.M., C.Z., and M.B.L. of the engineered proteases described (US Provisional Application No. 63/885,099). The remaining authors declare no competing interests.

Peer review information

Nature Communications thanks Zhongyue Yang and the other anonymous reviewer(s) for their contribution to the peer review of this work. A peer review file is available.

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