The amino acid sequences of proteins have evolved over billions of years, preserving their
structures and functions while responding to evolutionary forces. Are there conserved …

Interpreting changes in patient genomes, understanding how viruses evolve and
engineering novel protein function all depend on accurately predicting the functional …

Various protein properties are often illuminated using sequence comparisons of protein
homologs. For example, in analyses of the pyruvate kinase multiple sequence alignment …

Highlights•Quantification of the experimental fitness effects for thousands of
mutations.•Views into the biophysics of protein folding and function.•Mechanisms of …

To achieve the full potential of pharmacogenomics, one must accurately predict the
functional outcomes that arise from amino acid substitutions in proteins. Classically …

Functional conservation is known to constrain protein evolution. Nevertheless, the long-term
divergence patterns of proteins maintaining the same molecular function and the possible …

Human mutations often cause amino acid changes (variants) that can alter protein function
or stability. Some variants fall at protein positions that experimentally exhibit “rheostatic” …

Unsupervised sequence models for protein fitness have emerged as powerful tools for
protein design in order to engineer therapeutics and industrial enzymes, yet they are …

To optimize proteins for particular traits holds great promise for industrial and
pharmaceutical purposes. Machine Learning is increasingly applied in this field to predict …

The mapping from genotype to phenotype to fitness typically involves multiple nonlinearities
that can transform the effects of mutations. For example, mutations may contribute additively …