STAR Protocols
Volume 3, Issue 2, 17 June 2022, 101254
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Protocol
A computational protein design protocol for optimization of the SARS-CoV-2 receptor-binding-motif affinity for human ACE2

https://doi.org/10.1016/j.xpro.2022.101254Get rights and content
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Highlights

  • SARS-CoV-2 positions 455, 493, 494, and 501 at the interface with hACE2 are designed

  • The design uses Proteus, a high-throughput computational protein design program

  • A physics-based energy function ranks sequences and conformations

  • An adaptive Monte Carlo protocol promotes the selection of good affinity sequences

Publisher's note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Summary

The present protocol describes the computational design of the SARS-CoV-2 receptor binding motif (RBD) to identify mutations that can potentially improve binding affinity for the human ACE2 (hACE2) receptor. We focus on four positions located at the interface with the hACE2 receptor in the RBD:hACE2 complex. We conduct the design with a high-throughput computational protein design (CPD) program, Proteus, incorporating an adaptive Monte Carlo (MC) protocol that promotes the selection of sequences with good binding affinities.

For complete details on the use and execution of this protocol, please refer to Polydorides and Archontis (2021).

Subject areas

Biophysics
Protein Biochemistry
Structural Biology

Data and code availability

This study did not generate new code. The source code (Proteus3.0) is available at https://proteus.polytechnique.fr.

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