Abstract: Methods and systems for designing proteins are disclosed, as well as proteins and protein assemblies designed. A computing device can determine a protein repeating unit that includes one or more protein helices and one or more protein loops. The computing device can generate a protein backbone structure with a copy of the protein repeating unit. The computing device can determine whether a distance between a pair of helices of the protein backbone structure is between lower and upper distance thresholds. After determining that the distance between the pair of helices is between the lower and upper distance thresholds, the computing device can: generate a plurality of protein sequences based on the protein backbone structure, select a particular protein sequence of the plurality of protein sequences based on an energy landscape that has information about energy and distance from a target fold of the particular protein sequence, and generate an output based on the particular protein sequence.

Abstract: The invention relates to an engineered outer domain (eOD) of HIV gp120 and mutants thereof and methods of making and using the same. The mutant eODs may be advantageous for the elicitation of CD4-binding site (CD4bs)-directed broadly-neutralizing antibodies (bnAbs) and/or improve binding to mature VRC01 and/or improve binding to germline VRC01 and the germlines of other VH1-2 derived broadly-neutralizing antibodies. The mutant eODs may also include glycan-masking mutations on eOD. The present invention also includes fusions of eOD to various protein multimers to enhance immunogenicity as well as the design of cocktails of different eODs that represent the full diversity of HIV sequences within the VRC01 epitope and surroundings.

Abstract: The invention relates to an engineered outer domain (eOD) of HIV gp120 and mutants thereof and methods of making and using the same. The mutant eODs may be advantageous for the elicitation of CD4-binding site (CD4bs)-directed broadly-neutralizing antibodies (bnAbs) and/or improve binding to mature VRC01 and/or improve binding to germline VRC01 and the germlines of other VH1-2 derived broadly-neutralizing antibodies. The mutant eODs may also include glycan-masking mutations on eOD. The present invention also includes fusions of eOD to various protein multimers to enhance immunogenicity as well as the design of cocktails of different eODs that represent the full diversity of HIV sequences within the VRC01 epitope and surroundings.

Abstract: The invention relates to an engineered outer domain (eOD) of HIV gp120 and mutants thereof and methods of making and using the same. The mutant eODs may be advantageous for the elicitation of CD4-binding site (CD4bs)-directed broadly-neutralizing antibodies (bnAbs) and/or improve binding to mature VRC01 and/or improve binding to germline VRC01 and the germlines of other VH1-2 derived broadly-neutralizing antibodies. The mutant eODs may also include glycan-masking mutations on eOD. The present invention also includes fusions of eOD to various protein multimers to enhance immunogenicity as well as the design of cocktails of different eODs that represent the full diversity of HIV sequences within the VRC01 epitope and surroundings.

Abstract: Methods and systems for designing proteins are disclosed, as well as proteins and protein assemblies designed. A comparing device can determine a protein repeating unit that includes one or more protein helices and one or more protein loops. The computing device can generate a protein backbone structure with a copy of the protein repeating unit. The computing device can determine whether a distance between a pair of helices of the protein backbone structure is between lower and upper distance thresholds. After determining that the distance between the pair of helices is between the lower and upper distance thresholds, the computing device can generate a plurality of protein sequences based on the protein backbone structure, select a particular protein sequence of the plurality of protein sequences based on an energy landscape that has information about energy and distance from a target fold of the particular protein sequence, and generate an output based on the particular protein sequence.

Abstract: The invention relates to an engineered outer domain (eOD) of HIV gp120 and mutants thereof and methods of making and using the same. The mutant eODs may be advantageous for the elicitation of CD4-binding site (CD4bs)-directed broadly-neutralizing antibodies (bnAbs) and/or improve binding to mature VRC01 and/or improve binding to germline VRC01 and the germlines of other VH1-2 derived broadly-neutralizing antibodies. The mutant eODs may also include glycan-masking mutations on eOD. The present invention also includes fusions of eOD to various protein multimers to enhance immunogenicity as well as the design of cocktails of different eODs that represent the full diversity of HIV sequences within the VRC01 epitope and surroundings.

Abstract: The invention relates to an engineered outer domain (eOD) of HIV gp120 and mutants thereof and methods of making and using the same. The mutant eODs may be advantageous for the elicitation of CD4-binding site (CD4bs)-directed broadly-neutralizing antibodies (bnAbs) and/or improve binding to mature VRC01 and/or improve binding to germline VRC01 and the germlines of other VH1-2 derived broadly-neutralizing antibodies. The mutant eODs may also include glycan-masking mutations on eOD. The present invention also includes fusions of eOD to various protein multimers to enhance immunogenicity as well as the design of cocktails of different eODs that represent the full diversity of HIV sequences within the VRC01 epitope and surroundings.