Self-Assembling Protein Nanostructures

Abstract

Synthetic nanostructures, proteins that are useful, for example, in making synthetic nanostructures, and methods for designing such synthetic nanostructures are disclosed herein.

1 - 25 . (canceled) 
     
     
         26 . A method, comprising:
 generating a plurality of representations of a first protein building block using a computing device;   generating a plurality of representations of a second protein building block using the computing device, wherein the first protein building block differs from the second protein building block;   generating an arrangement of the plurality of representations of the first protein building block and the plurality of representations of the second protein building block according to symmetric operations of a designated mathematical symmetry group using the computing device; computationally determining a docked configuration of the arrangement of the plurality of representations of the first protein building block and the plurality of representations of the second protein building block by at least generating at least one interface for each protein building block of the arrangement that is suitable for computational protein-protein interface design using the computing device;   computationally modifying amino acid sequences of the plurality of representations of the first protein building block and the plurality of representations of the second protein building block in the docked configuration to specify a plurality of representations of protein-protein interfaces, wherein the plurality of representations of protein-protein interfaces comprise one or more representations of protein-protein interfaces between the first protein building block and the second protein building block that are energetically favorable to drive self-assembly of the protein building blocks comprising the modified amino acid sequences to the docked configuration using the computing device; and   generating an output of the computing device that is based on at least one representation of the group consisting of: a representation of the docked configuration, at least one representation of the plurality of representations of the protein-protein interfaces, and at least one representation of the representations of the first protein building block and the representations of the second protein building block having modified amino acid sequences.   
     
     
         27 . The method of  claim 26 , where each of the first and second protein building blocks comprise a synthetic polypeptide. 
     
     
         28 . The method of  claim 26 , where each of the first and second protein building blocks comprise a protein multimer that shares an axis of symmetry with the designated mathematical symmetry group. 
     
     
         29 . The method of  claim 26 , where the designated mathematical symmetry group conforms to a symmetry selected from tetrahedral point group symmetry, octahedral point group symmetry, and icosahedral point group symmetry. 
     
     
         30 . The method of  claim 26 , where generating the arrangement of the plurality of representations of the first protein building block and the plurality of representations of the second protein building block comprises computationally aligning symmetry axes of the first protein building block and the second protein building block with at least one axis in the designated mathematical symmetry group. 
     
     
         31 . The method of  claim 30 , wherein determining a docked configuration of the plurality of the first and second protein building blocks further comprises: sampling rotational degrees of freedom and translational degrees of freedom for each of the first and second protein building blocks. 
     
     
         32 . The method of  claim 31 , wherein sampling the rotational degrees of freedom and the translational degrees of freedom comprises:
 selecting a rotational value for a rotational degree of freedom for each of the first and second protein building blocks;   selecting a translational value for a translational degree of freedom for each of the first and second protein building blocks;   determining a sampled representation of the first protein building block based on the selected rotational value for the first protein building block and the selected translational value for the first protein building block;   determining a sampled representation of the second protein building block based on the selected rotational value for the second protein building block and the selected translational value for the second protein building block; and   determining a designability measure for the docked configuration using the sampled representation of the first protein building block and the sampled representation of the second protein building block.   
     
     
         33 . The method of  claim 32 , wherein determining the designability measure of the docked configuration comprises determining a number of beta carbon contacts within a specified distance threshold between the sampled representation of the first protein building block and the sampled representation of the second protein building block in the docked configuration based on the values of the selected rotational and translational degrees of freedom. 
     
     
         34 . The method of  claim 26 , wherein computationally modifying the amino acid sequences of the plurality of representations of the first protein building block and the plurality of representations of the second protein building block comprises selecting a selected representation of one or more amino acid sequences associated with a representation of at least one protein building block of the plurality of representations of the first protein building block and the plurality of representations of the second protein building block. 
     
     
         35 . The method of  claim 34 , wherein computationally modifying the amino acid sequences of the plurality of representations of the first protein building block and the plurality of representations of the second protein building block comprises computationally mutating an amino acid sequence of the selected representation of one or more amino acid sequences. 
     
     
         36 . The method of  claim 26 , wherein computationally modifying the amino acid sequences of the plurality of representations of the first protein building block and the plurality of representations of the second protein building block comprises evaluating an energy of an amino acid mutation using a computational score function.