Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for performing protein structure prediction. In one aspect, a method comprises generating a distance map for a given protein, wherein the given protein is defined by a sequence of amino acid residues arranged in a structure, wherein the distance map characterizes estimated distances between the amino acid residues in the structure, comprising: generating a plurality of distance map crops, wherein each distance map crop characterizes estimated distances between (i) amino acid residues in each of one or more respective first positions in the sequence and (ii) amino acid residues in each of one or more respective second positions in the sequence in the structure of the protein, wherein the first positions are a proper subset of the sequence; and generating the distance map for the given protein using the plurality of distance map crops.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for performing protein structure prediction. In one aspect, a method comprises, at each of one or more iterations: determining an alternative predicted structure of a given protein defined by alternative values of structure parameters; processing, using a geometry neural network, a network input comprising: (i) a representation of a sequence of amino acid residues in the given protein, and (ii) the alternative values of the structure parameters, to generate an output characterizing an alternative geometry score that is an estimate of a similarity measure between the alternative predicted structure and the actual structure of the given protein.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for performing protein structure prediction. In one aspect, a method comprises generating a distance map for a given protein, wherein the given protein is defined by a sequence of amino acid residues arranged in a structure, wherein the distance map characterizes estimated distances between the amino acid residues in the structure, comprising: generating a plurality of distance map crops, wherein each distance map crop characterizes estimated distances between (i) amino acid residues in each of one or more respective first positions in the sequence and (ii) amino acid residues in each of one or more respective second positions in the sequence in the structure of the protein, wherein the first positions are a proper subset of the sequence; and generating the distance map for the given protein using the plurality of distance map crops.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for designing a protein by jointly generating an amino acid sequence and a structure of the protein. In one aspect, a method comprises: generating data defining the amino acid sequence and the structure of the protein using a protein design neural network, comprising, for a plurality of positions in the amino acid sequence: receiving the current representation of the protein as of the current position: processing the current representation of the protein using the protein design neural network to generate design data for the current position that comprises: (i) data identifying an amino acid at the current position, and (ii) a set of structure parameters for the current position; and updating the current representation of the protein using the design data for the current position.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for determining a predicted structure of a protein that is specified by an amino acid sequence. In one aspect, a method comprises: obtaining an initial embedding and initial values of structure parameters for each amino acid in the amino acid sequence, wherein the structure parameters for each amino acid comprise location parameters that specify a predicted three-dimensional spatial location of the amino acid in the structure of the protein; and processing a network input comprising the initial embedding and the initial values of the structure parameters for each amino acid in the amino acid sequence using a folding neural network to generate a network output comprising final values of the structure parameters for each amino acid in the amino acid sequence.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for performing protein structure prediction and protein domain segmentation. In one aspect, a method comprises generating a plurality of predicted structures of a protein, wherein generating a predicted structure of the protein comprises: updating initial values of a plurality of structure parameters of the protein, comprising, at each of a plurality of update iterations: determining a gradient of a quality score for the current values of the structure parameters with respect to the current values of the structure parameters; and updating the current values of the structure parameters using the gradient.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for determining a predicted structure of a protein that is specified by an amino acid sequence. In one aspect, a method comprises: obtaining a multiple sequence alignment for the protein; determining, from the multiple sequence alignment and for each pair of amino acids in the amino acid sequence of the protein, a respective initial embedding of the pair of amino acids; processing the initial embeddings of the pairs of amino acids using a pair embedding neural network comprising a plurality of self-attention neural network layers to generate a final embedding of each pair of amino acids; and determining the predicted structure of the protein based on the final embedding of each pair of amino acids.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for predicting a structure of a protein that comprises a plurality of amino acid chains using a protein structure prediction neural network, where each chain comprises a respective sequence of amino acids. In one aspect, a method comprises: receiving a network input for the protein structure prediction neural network, wherein the network input characterizes the protein; processing the network input characterizing the protein using the protein structure prediction neural network to generate a network output that characterizes a predicted structure of the protein; and determining the predicted structure of the protein based on the network output.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for determining a predicted structure of a protein that is specified by an amino acid sequence. In one aspect, a method comprises: obtaining a multiple sequence alignment for the protein; determining, from the multiple sequence alignment and for each pair of amino acids in the amino acid sequence of the protein, a respective initial embedding of the pair of amino acids; processing the initial embeddings of the pairs of amino acids using a pair embedding neural network comprising a plurality of self-attention neural network layers to generate a final embedding of each pair of amino acids; and determining the predicted structure of the protein based on the final embedding of each pair of amino acids.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for predicting a structure of a protein that comprises a plurality of amino acid chains.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for performing protein design. In one aspect, a method comprises: processing an input characterizing a target protein structure of a target protein using an embedding neural network having a plurality of embedding neural network parameters to generate an embedding of the target protein structure of the target protein; determining a predicted amino acid sequence of the target protein based on the embedding of the target protein structure, comprising: conditioning a generative neural network having a plurality of generative neural network parameters on the embedding of the target protein structure; and generating, by the generative neural network conditioned on the embedding of the target protein structure, a representation of the predicted amino acid sequence of the target protein.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for determining a predicted structure of a protein. According to one aspect, there is provided a method comprising maintaining graph data representing a graph of the protein; obtaining a respective pair embedding for each edge in the graph; processing the pair embeddings using a sequence of update blocks, wherein each update block performs operations comprising, for each edge in the graph: generating a respective representation of each of a plurality of cycles in the graph that include the edge by, for each cycle, processing embeddings for edges in the cycle in accordance with the values of the update block parameters of the update block to generate the representation of the cycle; and updating the pair embedding for the edge using the representations of the cycles in the graph that include the edge.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for predicting a structure of a protein comprising one or more chains. In one aspect, a method comprises, at each subsequent iteration after a first iteration in a sequence of iterations: obtaining a network input for the subsequent iteration that characterizes the protein; generating, from (i) structure parameters generated at a preceding iteration that precedes the subsequent iteration in the sequence, (ii) one or intermediate outputs generated by the protein structure prediction neural network while generating the structure parameters at the last iteration, or (iii) both, features for the subsequent iteration; and processing the features and the network input for the subsequent iteration using the protein structure prediction neural network to generate structure parameters for the subsequent iteration that define another predicted structure for the protein.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for training neural networks to predict the structure of a protein.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for predicting a structure of a protein comprising one or more chains. In one aspect, a method comprises: obtaining an initial multiple sequence alignment (MSA) representation; obtaining a respective initial pair embedding for each pair of amino acids in the protein; processing an input comprising the initial MSA representation and the initial pair embeddings using an embedding neural network to generate an output that comprises a final MSA representation and a respective final pair embedding for each pair of amino acids in the protein; and determining a predicted structure of the protein using the final MSA representation, the final pair embeddings, or both.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for performing protein structure prediction. In one aspect, a method comprises generating a distance map for a given protein, wherein the given protein is defined by a sequence of amino acid residues arranged in a structure, wherein the distance map characterizes estimated distances between the amino acid residues in the structure, comprising: generating a plurality of distance map crops, wherein each distance map crop characterizes estimated distances between (i) amino acid residues in each of one or more respective first positions in the sequence and (ii) amino acid residues in each of one or more respective second positions in the sequence in the structure of the protein, wherein the first positions are a proper subset of the sequence; and generating the distance map for the given protein using the plurality of distance map crops.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for determining a predicted structure of a protein that is specified by an amino acid sequence. In one aspect, a method comprises: obtaining an initial embedding and initial values of structure parameters for each amino acid in the amino acid sequence, wherein the structure parameters for each amino acid comprise location parameters that specify a predicted three-dimensional spatial location of the amino acid in the structure of the protein; and processing a network input comprising the initial embedding and the initial values of the structure parameters for each amino acid in the amino acid sequence using a folding neural network to generate a network output comprising final values of the structure parameters for each amino acid in the amino acid sequence.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for performing protein structure prediction and protein domain segmentation. In one aspect, a method comprises generating a plurality of predicted structures of a protein, wherein generating a predicted structure of the protein comprises: updating initial values of a plurality of structure parameters of the protein, comprising, at each of a plurality of update iterations: determining a gradient of a quality score for the current values of the structure parameters with respect to the current values of the structure parameters; and updating the current values of the structure parameters using the gradient.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for performing protein structure prediction. In one aspect, a method comprises, at each of one or more iterations: determining an alternative predicted structure of a given protein defined by alternative values of structure parameters; processing, using a geometry neural network, a network input comprising: (i) a representation of a sequence of amino acid residues in the given protein, and (ii) the alternative values of the structure parameters, to generate an output characterizing an alternative geometry score that is an estimate of a similarity measure between the alternative predicted structure and the actual structure of the given protein.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for determining a predicted structure of a protein that is specified by an amino acid sequence. In one aspect, a method comprises: obtaining a multiple sequence alignment for the protein; determining, from the multiple sequence alignment and for each pair of amino acids in the amino acid sequence of the protein, a respective initial embedding of the pair of amino acids; processing the initial embeddings of the pairs of amino acids using a pair embedding neural network comprising a plurality of self-attention neural network layers to generate a final embedding of each pair of amino acids; and determining the predicted structure of the protein based on the final embedding of each pair of amino acids.