SARS-CoV-2 has evolved to acquire mutations on the spike protein—the part of the virus that protrudes from its surface and latches onto cells to infect them—that enhance the coronavirus' ability to bind to human cells or evade antibodies. A new study from the Centers for Genomics and Systems Biology at New York University and NYU Abu Dhabi uses computational modeling to assess the biological significance of spike protein mutations, uncovering versions of the virus that bind more tightly or resist antibodies and offering a promising public health surveillance tool.