Foldy: An open-source web application for interactive protein structure analysis

Jacob B Roberts; Alberto A Nava; Allison N Pearson; Matthew R Incha; Luis E Valencia; Melody Ma; Abhay Rao; Jay D Keasling

doi:10.1371/journal.pcbi.1011171

Foldy: An open-source web application for interactive protein structure analysis

PLoS Comput Biol. 2024 Feb 2;20(2):e1011171. doi: 10.1371/journal.pcbi.1011171. eCollection 2024 Feb.

Authors

Jacob B Roberts^{1

2

3}, Alberto A Nava^{1

2

4}, Allison N Pearson^{1

2

5}, Matthew R Incha^{1

2

5}, Luis E Valencia^{1

2

4}, Melody Ma⁶, Abhay Rao³, Jay D Keasling^{1

2

3

4

7

8}

Affiliations

¹ Joint BioEnergy Institute, Lawrence Berkeley National Laboratory, Emeryville, California, United States of America.
² Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
³ Department of Bioengineering, University of California, Berkeley, Berkeley, California, United States of America.
⁴ Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, California, United States of America.
⁵ Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, United States of America.
⁶ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, United States of America.
⁷ Center for Synthetic Biochemistry, Shenzhen Institutes for Advanced Technologies, Shenzhen, People's Republic of China.
⁸ The Novo Nordisk Foundation Center for Biosustainability, Technical University Denmark, Kemitorvet, Denmark.

Abstract

Foldy is a cloud-based application that allows non-computational biologists to easily utilize advanced AI-based structural biology tools, including AlphaFold and DiffDock. With many deployment options, it can be employed by individuals, labs, universities, and companies in the cloud without requiring hardware resources, but it can also be configured to utilize locally available computers. Foldy enables scientists to predict the structure of proteins and complexes up to 6000 amino acids with AlphaFold, visualize Pfam annotations, and dock ligands with AutoDock Vina and DiffDock. In our manuscript, we detail Foldy's interface design, deployment strategies, and optimization for various user scenarios. We demonstrate its application through case studies including rational enzyme design and analyzing proteins with domains of unknown function. Furthermore, we compare Foldy's interface and management capabilities with other open and closed source tools in the field, illustrating its practicality in managing complex data and computation tasks. Our manuscript underlines the benefits of Foldy as a day-to-day tool for life science researchers, and shows how Foldy can make modern tools more accessible and efficient.

Copyright: © 2024 Roberts et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH terms

Amino Acids
Humans
Proteins*
Software*

Substances

Proteins
Amino Acids

Grants and funding

This work was part of the DOE Joint BioEnergy Institute (jbei.org) supported by the U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research, through contract DE-AC02-05CH11231 between Lawrence Berkeley National Laboratory and the U.S. Department of Energy and by a Department of Energy Office of Science Distinguished Scientist Award to J.D.K. J.B.R. was supported in part by a fellowship award under contract [FA9550-21-F-0003] through the National Defense Science and Engineering Graduate (NDSEG) Fellowship Program, sponsored by the Air Force Research Laboratory (AFRL), the Office of Naval Research (ONR) and the Army Research Office (ARO). A.A.N. was supported by a National Science Foundation Graduate Research Fellowship, fellow ID [2018253421]. The views and opinions of the authors expressed herein do not necessarily state or reflect those of the United States Government or any agency thereof. Neither the United States Government nor any agency thereof, nor any of their employees,makes any warranty, expressed or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.