Protein complex structure prediction from cryo-electron microscopy (cryo-em) density maps

A non-transitory computer-readable medium having computer-executable instructions stored thereon that, in response to execution by one or more processors of a computing system, cause the computing system to determine a molecular structure of a protein by performing actions comprising:

• receiving, by the computing system, voxel data representing electron density obtained via cryo-electron microscopy;
• using, by the computing system, one or more neural networks to predict one or more likelihoods for each voxel;
• determining, by the computing system, a backbone structure based on the predicted likelihoods;
• mapping, by the computing system, amino acid sequences to the backbone structure based on the predicted likelihoods, wherein mapping the amino acid sequences to the backbone structure based on the predicted likelihoods includes conducting an alignment technique that uses a reward function and a gap penalty;
• determining, by the computing system, locations of carbon, nitrogen, and oxygen atoms within the backbone structure based on the predicted likelihoods;
• determining, by the computing system, side-chain atoms based on the predicted backbone structure and the amino acid sequences to complete the molecular structure;
• and
• storing, by the computing system, the determined molecular structure.

A computing system configured to perform actions for determining a molecular structure of a protein, the actions comprising:

• receiving, by the computing system, voxel data representing electron density obtained via cryo-electron microscopy;
• using, by the computing system, one or more neural networks to predict one or more likelihoods for each voxel;
• determining, by the computing system, a backbone structure based on the predicted likelihoods;
• mapping, by the computing system, amino acid sequences to the backbone structure based on the predicted likelihoods, wherein mapping the amino acid sequences to the backbone structure based on the predicted likelihoods includes conducting an alignment technique that uses a reward function and a gap penalty;
• determining, by the computing system, locations of carbon, nitrogen, and oxygen atoms within the backbone structure based on the predicted likelihoods;
• determining, by the computing system, side-chain atoms based on the predicted backbone structure and the amino acid sequences to complete the molecular structure;
• and
• storing, by the computing system, the molecular structure in a non-transitory computer-readable medium.