CRISPro: An Automated Pipeline for Protein Conformation Stabilization by Proline
Reda Rawi1, Chen-Hsiang Shen1, Peter D Kwong1,2
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases , National Institutes of Health , Bethesda , Maryland 20892 , United States.
Journal of Chemical Information and Modeling
|October 6, 2018
Summary
A new tool, CRISPro, automatically designs proline mutations to stabilize specific protein conformations, enhancing immunogen design and antibody isolation for vaccine development.
Area of Science:
- Structural biology
- Immunology
- Computational biology
Background:
- Protein conformation influences immunogen properties like antigenicity and immunogenicity.
- Engineering specific conformations can enhance immunogen efficacy.
- Proline mutations are effective for conformational stabilization but designing them is challenging.
Purpose of the Study:
- To develop an automated computational tool for designing proline mutations to stabilize target protein conformations.
- To provide a resource for researchers engineering immunogens and designing serologic probes.
Main Methods:
- CRISPro takes structural coordinates of target and alternative conformations as input.
- It predicts proline mutation sites based on phi-psi angles, secondary structure compatibility, and steric constraints.
- The tool identifies residues compatible with the target conformation but not alternative ones.
Main Results:
- CRISPro successfully identifies potential proline mutation sites for conformational stabilization.
- The tool provides a list of residue positions for targeted protein engineering.
- Enables the design of immunogens with enhanced antigenicity and immunogenicity.
Conclusions:
- CRISPro automates the design of conformationally stabilized immunogens.
- The tool facilitates the creation of specific serologic probes for antibody isolation.
- CRISPro advances protein engineering for vaccine and antibody discovery applications.
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