Methods of constructing and screening libraries of peptide structures

A method for producing a library of independent protein secondary structures having low structural redundancy, said method consisting essentially of the following sequential steps:

• (i) executing a computer program to thereby obtain a plurality of amino acid sequences of different proteins from bioinformatic data source(s) wherein the sequences are predicted to form secondary structures and/or assemblies of secondary structures in their native contexts;
• (ii) executing a computer program to simultaneously select from (i) a plurality of amino acid sequences of the different proteins, wherein the simultaneously-selected sequences each consist of a single segment of a protein corresponding to a hydrophobic folding unit is predicted to form a secondary structures independent of any other part of the protein from which it is derived when isolated from those other parts of the protein;
• (iii) executing a computer program to thereby identify sequences in the plurality at (ii) that are predicted to form redundant secondary structures and removing or deleting sufficient sequences predicted to form the redundant secondary structures to thereby select a plurality of amino acid sequences predicted to form non-redundant secondary structures independent of any other part of the proteins from which they are derived when isolated from those other parts of the proteins, wherein no more than five of said sequences are predicted to form the same secondary structure;
• and
• (iv) chemically-synthesizing a plurality of peptides that each consist essentially of a sequence selected at (iii) that is predicted to form a non-redundant secondary structure independent of any other part of the protein from which it is derived when isolated from those other parts of the protein;
• and
• (v) displaying the plurality of peptides chemically-synthesized at (iv) such that the displayed peptides form secondary structures independent of other parts of the proteins, thereby producing a library of independent protein secondary structures having low structural redundancy.

A method for producing a library of independent protein secondary structures having low structural redundancy, said method consisting essentially of the following sequential steps:

• (i) executing a computer program to thereby obtain a plurality of amino acid sequences of different proteins from bioinformatic data source(s) wherein the sequences are predicted to form secondary structures and/or assemblies of secondary structures in their native contexts;
• (ii) executing a computer program to simultaneously select from (i) a plurality of amino acid sequences of the different proteins, wherein the simultaneously-selected sequences each consist of a single segment of a protein corresponding to a hydrophobic folding unit is predicted to form a secondary structures independent of any other part of the protein from which it is derived when isolated from those other parts of the protein;
• (iii) executing a computer program to identify sequences in the plurality at (ii) which are redundant and removing or deleting the redundant sequences to thereby select for a non-redundant plurality of sequences;
• (iv) chemically-synthesizing a plurality of peptides that each consist essentially of a sequence selected at (iii) which is non-redundant and that is predicted to form a secondary structure independent of any other part of the protein from which it is derived when isolated from those other parts of the protein;
• and
• (v) displaying the plurality of peptides chemically-synthesized at (iv) such that the displayed peptides form secondary structures independent of their native contexts, thereby producing a library of independent protein secondary structures having low structural redundancy.

A method for producing a library of independent protein secondary structures, said method comprising:

• (i) executing a computer program to thereby identify a plurality of amino acid sequences of different proteins from bioinformatic data source(s) wherein the sequences are capable of folding independently from other parts of the proteins in which they are contained in their native contexts;
• (ii) executing a computer program to simultaneously select from (i) a plurality of amino acid sequences of different proteins that arc each consist of a single segment of a protein corresponding to a hydrophobic folding unit capable of folding independently from other parts of the proteins from which they are derived when isolated from those other parts of the proteins;
• (iii) size-selecting those sequences selected at (ii) to thereby select a sub-set of sequences having the average length of an independent protein fold;
• (iv) executing a computer program to identify redundant sequences in the sub-set of sequences selected at (iii) and removing or deleting redundant sequences to thereby select for a non-redundant plurality of amino acid sequences;
• (v) chemically-synthesizing a plurality of peptides that each consist essentially of a sequence selected at (iv) which is non-redundant and capable of folding independently of any other part of the protein from which it is derived when isolated from other parts of the protein;
• and;
• (vi) displaying the plurality of peptides chemically-synthesized at (v) such that the displayed peptides form secondary structures and/or folds independent of other parts of the proteins, thereby producing a library of independent protein secondary structures.

A method for producing a library of independent protein secondary structures, said method comprising:

• (i) executing a computer program to thereby identify a plurality of amino acid sequences of different proteins from bioinformatic data source(s) wherein the sequences are capable of folding independently from other parts of the proteins in which they are contained in their native contexts;
• (ii) executing a computer program to simultaneously select from (i) a plurality of amino acid sequences of the different proteins that each consist of a single segment of a protein corresponding to a hydrophobic folding unit and are each capable of folding independently from other parts of the proteins from which they are derived when isolated from those other parts of the proteins;
• (iii) size-selecting those sequences at (ii) to thereby select a sub-set of sequences having the average length of an independent protein fold;
• (iv) executing a computer program to identify redundant sequences in the sub-set of sequences selected at (iii) and removing or deleting redundant sequences to thereby select for a non-redundant plurality of amino acid sequences;
• (v) identifying related sequences to the non-redundant plurality of amino acid sequences at (iv) and adding those related sequences to the non-redundant plurality of amino acid sequences to thereby produce a diverse pool of amino acid sequences;
• (vi) chemically-synthesizing a plurality of peptides that each consist essentially of a sequence selected from the diverse pool of amino acid sequences produced at (v);
• and
• (vii) displaying the plurality of peptides chemically-synthesized at (vi) such that the displayed peptides form secondary structures and/or folds independent of any other parts of the protein from which they are derived when isolated from those other parts of the proteins their native contexts, thereby producing a library of independent protein secondary structures.