Toolkit/BROAD

BROAD

Computational Method·Research·Since 2018

Taxonomy: Technique Branch / Method. Workflows sit above the mechanism and technique branches rather than replacing them.

Summary

BROAD is a computational protein design method that combines Rosetta-based structure modeling, machine learning, and integer linear programming to improve design search beyond Rosetta sampling alone. It was demonstrated in antibody design to increase the predicted HIV neutralization breadth of VRC23 across a panel of 180 divergent viral strains.

Usefulness & Problems

Why this is useful

BROAD is useful for protein design problems in which conventional Rosetta multistate design is limited by sampling and optimization across many target states. In the reported study, it increased predicted antibody breadth and reached 100% predicted binding across 180 HIV strains, indicating utility for broad-specificity design tasks.

Problem solved

BROAD was developed to overcome limitations in Rosetta sampling methods during multistate protein design. The demonstrated application addressed the challenge of increasing predicted HIV antibody neutralization breadth against diverse viral strains.

Problem links

Need conditional recombination or state switching

Derived

BROAD is a computational protein design method that integrates Rosetta-based structural modeling with machine learning and integer linear programming. It was developed to overcome sampling limitations in Rosetta and was demonstrated on antibody design to increase predicted HIV neutralization breadth.

Taxonomy & Function

Implementation Constraints

cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationoperating role: builder

BROAD integrates structure-based modeling in the Rosetta software suite with machine learning and integer linear programming. The reported implementation was applied to multistate antibody design for VRC23 against a panel of divergent HIV strains, but the provided evidence does not specify model features, solver details, or required input formats.

The supplied evidence is limited to a single 2018 study and a computational antibody-design demonstration. The available evidence does not report experimental validation, implementation details beyond the algorithmic components, or performance in non-antibody protein systems.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Supporting Sources

Ranked Claims

Claim 1benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 2benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 3benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 4benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 5benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 6benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 7benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 8benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 9benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 10benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 11benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 12benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 13benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 14benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 15benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 16benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 17benchmark performancesupports2018Source 1needs review

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.
predicted binding coverage 100 %viral strain panel size 180 strains
Claim 18comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 19comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 20comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 21comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 22comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 23comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 24comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 25comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 26comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 27comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 28comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 29comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 30comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 31comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 32comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 33comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 34comparative performancesupports2018Source 1needs review

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.
Claim 35generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 36generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 37generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 38generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 39generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 40generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 41generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 42generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 43generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 44generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 45generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 46generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 47generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 48generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 49generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 50generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 51generalizabilitysupports2018Source 1needs review

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.
Claim 52method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 53method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 54method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 55method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 56method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 57method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 58method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 59method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 60method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 61method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 62method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 63method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 64method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 65method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 66method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 67method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 68method descriptionsupports2018Source 1needs review

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.
Claim 69predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 70predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 71predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 72predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 73predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 74predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 75predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 76predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 77predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 78predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 79predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 80predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 81predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 82predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 83predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 84predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 85predicted not experimentally testedsupports2018Source 1needs review

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.
Claim 86sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 87sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 88sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 89sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 90sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 91sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 92sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 93sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 94sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 95sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 96sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 97sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 98sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 99sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 100sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 101sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.
Claim 102sequence feature recoverysupports2018Source 1needs review

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.

Approval Evidence

1 source6 linked approval claimsfirst-pass slug broad
We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods. We demonstrate the effectiveness of this method, which we call BROAD

Source:

benchmark performancesupports

BROAD increased predicted breadth of antibody VRC23 against a panel of 180 divergent HIV viral strains and achieved 100% predicted binding against that panel.

We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel.

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comparative performancesupports

BROAD significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison.

In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.

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generalizabilitysupports

The authors state that BROAD is general and can be extended easily to other protein systems.

Finally, our approach is general and can be extended easily to other protein systems.

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method descriptionsupports

BROAD is a computational approach that combines Rosetta-based structural modeling with machine learning and integer linear programming to overcome limitations in Rosetta sampling methods.

We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods.

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predicted not experimentally testedsupports

The modeled antibody variants were not tested in vitro, and the reported breadth increase is a prediction relative to wild-type antibody.

Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.

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sequence feature recoverysupports

Sequences recovered by BROAD recovered known binding motifs of broadly neutralizing anti-HIV antibodies.

We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies.

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Comparisons

Source-backed strengths

The method significantly outperformed state-of-the-art multistate design in Rosetta in the reported comparison. In the benchmark application, BROAD increased the predicted breadth of antibody VRC23 and achieved 100% predicted binding against a 180-strain HIV panel.

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In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly.

BROAD and computational design strategy address a similar problem space because they share recombination.

Shared frame: same top-level item type; shared target processes: recombination

Compared with FRASE

BROAD and FRASE address a similar problem space because they share recombination.

Shared frame: same top-level item type; shared target processes: recombination

BROAD and NCBI sequence screening for 2A/2A-like occurrence address a similar problem space because they share recombination.

Shared frame: same top-level item type; shared target processes: recombination

Strengths here: looks easier to implement in practice.

Ranked Citations

  1. 1.
    StructuralSource 1PLoS Computational Biology2018Claim 16Claim 17Claim 3

    Extracted from this source document.