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AlphaFold illuminates half of the dark human proteins.

ABSTRACT: We investigate the use of confidence scores to evaluate the accuracy of a given AlphaFold (AF2) protein model for drug discovery. Prediction of accuracy is improved by not considering confidence scores below 80 due to the effects of disorder. On a set of recent crystal structures, 95% are likely to have accurate folds. Conformational discordance in the training set has a much more significant effect on accuracy than sequence divergence. We propose criteria for models and residues that are possibly useful for virtual screening. Based on these criteria, AF2 provides models for half of understudied (dark) human proteins and two-thirds of residues in those models.

SUBMITTER: Binder JL

PROVIDER: S-EPMC10669925 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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AlphaFold illuminates half of the dark human proteins.

Binder Jessica L JL Berendzen Joel J Stevens Amy O AO He Yi Y Wang Jian J Dokholyan Nikolay V NV Oprea Tudor I TI

Current opinion in structural biology 20220416

We investigate the use of confidence scores to evaluate the accuracy of a given AlphaFold (AF2) protein model for drug discovery. Prediction of accuracy is improved by not considering confidence scores below 80 due to the effects of disorder. On a set of recent crystal structures, 95% are likely to have accurate folds. Conformational discordance in the training set has a much more significant effect on accuracy than sequence divergence. We propose criteria for models and residues that are possib ...[more]

PMID: 35439658

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