Incremental macromolecule construction methods

Claim 2

A computer-assisted method for modifying a structure using at least two blocks disposed between a starting point and an end point, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks; and (c) synthesizing the structure with the first one and second one of said blocks as specified by steps (a) and (b), respectively.

Claim 3

The method of claim 1, wherein said non-spatial parameter of step (a) or of said (b) is a local dielectric constant.

Claim 4

The method of claim 1, wherein said non-spatial parameter of step (a) or of said (b) is a hydrogen-bonding propensity.

Claim 5

The method of claim 1, wherein said non-spatial parameter of step (a) or of said (b) is a localized electrostatic charge.

Claim 6

The method of claim 1, further comprising a step (d) between steps (b) and (c) of incrementally adding a third one of said blocks to said first one of said blocks or to said second one of said blocks or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks, and wherein step (c) synthesizes the structure with the first one, the second one, and the third one of said blocks as specified by steps (a), (b) and (d).

Claim 7

The method of claim 1, wherein said blocks are selected from a library, wherein some of said blocks within said library contain peptide sequences.

Claim 8

The method of claim 1, wherein said blocks are selected from a library which provides, for each block therein, multiple precomputed parameters, including a first parameter for estimating dependence of energy on a second parameter (including conformational parameters) of said block.

Claim 9

A computer-assisted method for modifying a structure using at least two blocks to bridge the structure between a starting point and an end point, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks, said second one of said blocks ending at said end point; (c) synthesizing the structure with the first one and second one of said blocks as specified by steps (a) and (b), respectively, so that the first one and second one of said blocks bridge the structure between said starting point and said end point.

Claim 10

A computer-assisted method for modifying a structure using at least two blocks to bridge the structure between a starting point and an end point, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks, said second one of said blocks ending at said end point; (c) synthesizing the structure with the first one and second one of said blocks as specified by steps (a) and (b), respectively, so that the first one and second one of said blocks bridge the structure between said starting point and said end point.

Claim 11

A computer-assisted method for modifying a structure using n blocks to bridge the structure between a starting point and an end point, where n is a positive integer equal to or greater than 8, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said endpoint by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks; and (c) incrementally adding x one of said blocks, where x is a positive integer and is greater than 2, to said x-1 one of said blocks or to said x-2 one of said blocks by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said x one of said blocks; (d) repeating step (c) for incrementally adding x one of said blocks until x=n, so that n blocks bridge the structure between the starting point and the end point; (e) synthesizing the structure with the n blocks as specified by steps (a), (b), (c), and (d) so that the n blocks bridge the structure between said starting point and said end point.

Claim 12

A computer-assisted method for modifying a structure using n blocks to bridge the structure between a starting point and an end point, where n is a positive integer equal to or greater than 8, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said endpoint by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks; and (c) incrementally adding x one of said blocks, where x is a positive integer and is greater than 2, to said x-1 one of said blocks or to said x-2 one of said blocks by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said x one of said blocks; (d) repeating step (c) for incrementally adding x one of said blocks until x=n, so that n blocks bridge the structure between the starting point and the end point; (e) synthesizing the structure with the n blocks as specified by steps (a), (b), (c), and (d) so that the n blocks bridge the structure between said starting point and said end point.

Claim 13

The method of claim 9, wherein one or more of said n blocks is optimized using a local dielectric constant.

Claim 14

The method of claim 9, wherein one or more of said n blocks is optimized using hydrophobicity.

Claim 15

The method of claim 9, wherein one or more of said blocks is optimized using hydrogen bonding propensity.

Claim 16

The method of claim 9, wherein one or more of said n blocks is optimized using a dipole moment.

Claim 17

The method of claim 9, wherein one or more of said n blocks is optimized using a localized electrostatic charge.

Claim 18

The method of claim 9, further comprising a step (f) between step (d) and step (e) of performing steps (a), (b) and (c) using expert rules and/or rule-based merit selection.

Claim 19

The method of claim 9, wherein steps (a), (b), and (c) use an interactive computer process which, makes available to a user a graphics representation of said XYZ coordinates and said at least one non-spatial parameter, and performs ranking of blocks for steps (a), (b) and (c).

Claim 20

The method of claim 16, wherein said interactive computer process further comprises, permitting the user to exclude some of the blocks from consideration.

Claim 21

The method of claim 16, wherein said interactive computer process allows for the user to engage in backtracking in performing steps (a), (b) and/or (c).

Claim 22

The method of claim 9, wherein steps (a), (b) and/or (c) include the step of allowing the user to utilize look ahead optimization.

Claim 23

A computer-assisted method for modifying a structure using at least two blocks disposed between a starting point and an end point, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks peptide sequences of length n (wherein n is between 2 and 4 inclusive), said blocks being selected (at least in part) for fit with respect to said localized additional characteristics; (c) obtaining the information used in steps (a) and (b) from a library having peptide sequence information; and (d) synthesizing the structure with the first one and second one of said blocks as specified by steps (a) and (b), respectively.

Claim 24

A computer-assisted method for modifying a structure using at least two blocks disposed between a starting point and an end point, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks peptide sequences of length n (wherein n is between 2 and 4 inclusive), said blocks being selected (at least in part) for fit with respect to said localized additional characteristics; (c) obtaining the information used in steps (a) and (b) from a library having peptide sequence information; and (d) synthesizing the structure with the first one and second one of said blocks as specified by steps (a) and (b), respectively.

Claim 25

The method of claim 20, wherein said library of step (c) includes automatic mechanisms for updating said library with parameters for additional blocks as those parameters become available.

Claim 26

A computer-assisted method for modifying a structure using at least two blocks disposed between a starting point and an end point, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said endpoint by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks; and (c) performing (a) and (b) using expert rules and/or rule-based merit selection; and (d) synthesizing the structure with the first one and second one of said blocks as specified by steps (a) and (b), respectively.

Claim 27

A computer-assisted method for modifying a structure using at least two blocks disposed between a starting point and an end point, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said endpoint by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks; and (c) performing (a) and (b) using expert rules and/or rule-based merit selection; and (d) synthesizing the structure with the first one and second one of said blocks as specified by steps (a) and (b), respectively.

Claim 28

A computer-assisted method for modifying a structure using at least two blocks disposed between a starting point and an end point, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said endpoint by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks; (c) said first one and/or said second one of said blocks being selected by a method which includes the substeps of: (1) retrieving data from a library to define at least one candidate set for said first one and/or said second one of said blocks, (2) culling said candidate set of substep (1), using one or more non-spatial parameter(s), to remove unacceptable blocks from said candidate set to produce a reduced candidate set of blocks, and (3) optimizing adjustable parameters of blocks of said reduced candidate set of blocks disposed between said starting point and said end point; and (d) synthesizing the structure with the first one and second one of said blocks as specified by steps (a) and (b), respectively, so that the first one and second one of said blocks are disposed between said starting point and said end point.

Claim 29

A computer-assisted method for modifying a structure using at least two blocks disposed between a starting point and an end point, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said endpoint by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks; (c) said first one and/or said second one of said blocks being selected by a method which includes the substeps of: (1) retrieving data from a library to define at least one candidate set for said first one and/or said second one of said blocks, (2) culling said candidate set of substep (1), using one or more non-spatial parameter(s), to remove unacceptable blocks from said candidate set to produce a reduced candidate set of blocks, and (3) optimizing adjustable parameters of blocks of said reduced candidate set of blocks disposed between said starting point and said end point; and (d) synthesizing the structure with the first one and second one of said blocks as specified by steps (a) and (b), respectively, so that the first one and second one of said blocks are disposed between said starting point and said end point.

Claim 30

A computer-assisted method for modifying a structure using at least two blocks disposed between a starting point and an end point, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks; (c) said first one and/or said second one of said blocks being selected by a method which includes the substeps of; (1) retrieving data from a library to define a coordinate set of blocks, and (2) ranking said candidate set, and accordingly removing low-ranked blocks to provide a reduced candidate set of blocks disposed between said starting point and said end point; and (d) synthesizing the structure with the first one and second one of said blocks as specified by steps (a) and (b), respectively, so that the first one and second one of said blocks are disposed between said starting point and said end point.

Claim 31

A computer-assisted method for modifying a structure using at least two blocks disposed between a starting point and an end point, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks; (c) said first one and/or said second one of said blocks being selected by a method which includes the substeps of; (1) retrieving data from a library to define a coordinate set of blocks, and (2) ranking said candidate set, and accordingly removing low-ranked blocks to provide a reduced candidate set of blocks disposed between said starting point and said end point; and (d) synthesizing the structure with the first one and second one of said blocks as specified by steps (a) and (b), respectively, so that the first one and second one of said blocks are disposed between said starting point and said end point.

Claim 32

A computer-assisted method for modifying a structure using at least two blocks disposed between a starting point and an end point, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said endpoint by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks; (c) said first one and/or said second one of said blocks being selected by a method which includes the substeps of: (1) retrieving data from a library to define at least one candidate set for said first one and/or said second one of said blocks, (2) ranking said candidate set of blocks, and accordingly removing low-ranked blocks in said candidate set to provide a reduced candidate set of blocks, (3) optimizing adjustable parameters of blocks of said reduced candidate set of blocks, and (4) re-ranking said reduced candidate set of blocks, and accordingly removing low-ranked blocks from said reduced candidate set to provide a further-reduced candidate set of blocks disposed between said starting point and said end point; and (d) synthesizing the structure with the first one and second one of said blocks as specified by steps (a) and (b), respectively, so that the first one and second one of said blocks are disposed between said starting point and said end point.

Claim 33

A computer-assisted method for modifying a structure using at least two blocks disposed between a starting point and an end point, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said endpoint by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks; (c) said first one and/or said second one of said blocks being selected by a method which includes the substeps of: (1) retrieving data from a library to define at least one candidate set for said first one and/or said second one of said blocks, (2) ranking said candidate set of blocks, and accordingly removing low-ranked blocks in said candidate set to provide a reduced candidate set of blocks, (3) optimizing adjustable parameters of blocks of said reduced candidate set of blocks, and (4) re-ranking said reduced candidate set of blocks, and accordingly removing low-ranked blocks from said reduced candidate set to provide a further-reduced candidate set of blocks disposed between said starting point and said end point; and (d) synthesizing the structure with the first one and second one of said blocks as specified by steps (a) and (b), respectively, so that the first one and second one of said blocks are disposed between said starting point and said end point.

Claim 34

An interactive computer-assisted method for modifying a structure using at least two blocks disposed between a starting point and an end point, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks, using an interactive computer which, makes available to a user a graphics representation of information including XYZ coordinates and/or at least one non-spatial parameter of possible blocks for step (b) and the structure, and performs ranking of said possible blocks for step (b); and (c) synthesizing the structure with the first one and second one of said blocks as specified by steps (a) and (b), respectively, so that the first one and second one of said blocks are disposed between said starting point and said end point.

Claim 35

An interactive computer-assisted method for modifying a structure using at least two blocks disposed between a starting point and an end point, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks, using an interactive computer which, makes available to a user a graphics representation of information including XYZ coordinates and/or at least one non-spatial parameter of possible blocks for step (b) and the structure, and performs ranking of said possible blocks for step (b); and (c) synthesizing the structure with the first one and second one of said blocks as specified by steps (a) and (b), respectively, so that the first one and second one of said blocks are disposed between said starting point and said end point.

Claim 36

A computer-assisted process outputting at least two blocks to be disposed between a starting point and an end point of a structure, comprising the steps of: (a) mapping onto said starting point of said structure a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks by mapping to produce parameter of said second one of said blocks; and (c) outputting said first one and said second one of said blocks to be disposed between said starting point and said end point of said structure.

Claim 37

A computer-assisted process outputting at least two blocks to be disposed between a starting point and an end point of a structure, comprising the steps of: (a) mapping onto said starting point of said structure a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks by mapping to produce parameter of said second one of said blocks; and (c) outputting said first one and said second one of said blocks to be disposed between said starting point and said end point of said structure.

Claim 38

A product produced by a computer-assisted process, said product comprising a structure with a first block and a second block, said first and second blocks disposed between a starting point and an end point of said structure, said computer assisted process comprising the steps of: (a) mapping a structure having a starting point and an end point; (b) mapping onto said starting point the first block to produce information including XYZ coordinates and at least one non-spatial parameter of said first block; (c) incrementally adding the second block to said first block or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second block.

Claim 39

A product produced by a computer-assisted process, said product comprising a structure with a first block and a second block, said first and second blocks disposed between a starting point and an end point of said structure, said computer assisted process comprising the steps of: (a) mapping a structure having a starting point and an end point; (b) mapping onto said starting point the first block to produce information including XYZ coordinates and at least one non-spatial parameter of said first block; (c) incrementally adding the second block to said first block or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second block.

Claim 40

A product produced by a computer-assisted process, said product comprising a structure with a first block and a second block, said first and second blocks bridging the structure between a starting point and an end point of said structure, said computer assisted process comprising the steps of: (a) mapping the structure having a starting point and an end point; (b) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of the first block; (c) incrementally adding the second block to the first block or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of the second block, the second block ending at the end point.

Claim 41

A product produced by a computer-assisted process, said product comprising a structure with a first block and a second block, said first and second blocks bridging the structure between a starting point and an end point of said structure, said computer assisted process comprising the steps of: (a) mapping the structure having a starting point and an end point; (b) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of the first block; (c) incrementally adding the second block to the first block or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of the second block, the second block ending at the end point.

Claim 42

A product produced by a computer-assisted process, said product comprising a structure with n blocks, said n blocks bridging the structure between a starting point and an end point of said structure, where n is a positive integer equal to or greater than 2, said computer assisted process comprising the steps of: (a) mapping the structure having a starting point and an end point; (b) mapping onto said starting point a first one of said n blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said one of said blocks; (c) incrementally adding a second one of said n blocks to said first one of said n blocks or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said n blocks; (d) incrementally adding x one of said n blocks, where x is a positive integer and is greater than 2, to said x-1 one of said n blocks or to said x-2 one of said n blocks by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said x one of said n blocks; (e) repeating step (d) for incrementally adding x one of said n blocks until x=n, so that n blocks bridge the structure between the starting point and the end point.

Claim 43

A product produced by a computer-assisted process, said product comprising a structure with n blocks, said n blocks bridging the structure between a starting point and an end point of said structure, where n is a positive integer equal to or greater than 2, said computer assisted process comprising the steps of: (a) mapping the structure having a starting point and an end point; (b) mapping onto said starting point a first one of said n blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said one of said blocks; (c) incrementally adding a second one of said n blocks to said first one of said n blocks or to said end point by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said n blocks; (d) incrementally adding x one of said n blocks, where x is a positive integer and is greater than 2, to said x-1 one of said n blocks or to said x-2 one of said n blocks by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said x one of said n blocks; (e) repeating step (d) for incrementally adding x one of said n blocks until x=n, so that n blocks bridge the structure between the starting point and the end point.

Claim 44

A computer-assisted process outputting n blocks for modifying a structure, where the n blocks bridge the structure between a starting point and an end point, where n is a positive integer equal to or greater than 2, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said endpoint by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks; (c) incrementally adding x one of said blocks, where x is a positive integer and is greater than 2, to said x-1 one of said blocks or to said x-2 one of said blocks by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said x one of said blocks; (d) repeating step (c) for incrementally adding x one of said blocks until x=n, so that n blocks bridge the structure between the starting point and the end point; (e) outputting the structure with the n blocks as specified by steps (a), (b), (c), and (d) so that the n blocks bridge the structure between said starting point and said end point.

Claim 45

A computer-assisted process outputting n blocks for modifying a structure, where the n blocks bridge the structure between a starting point and an end point, where n is a positive integer equal to or greater than 2, comprising the steps of: (a) mapping onto said starting point a first one of said blocks to produce information including XYZ coordinates and at least one non-spatial parameter of said first one of said blocks; (b) incrementally adding a second one of said blocks to said first one of said blocks or to said endpoint by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said second one of said blocks; (c) incrementally adding x one of said blocks, where x is a positive integer and is greater than 2, to said x-1 one of said blocks or to said x-2 one of said blocks by mapping to produce information including XYZ coordinates and at least one non-spatial parameter of said x one of said blocks; (d) repeating step (c) for incrementally adding x one of said blocks until x=n, so that n blocks bridge the structure between the starting point and the end point; (e) outputting the structure with the n blocks as specified by steps (a), (b), (c), and (d) so that the n blocks bridge the structure between said starting point and said end point.