Abstract
Despite the central role that antibodies play in modern medicine, there is currently no way to rationally design novel antibodies to bind a specific epitope on a target. Instead, antibody discovery currently involves time-consuming immunization of an animal or library screening approaches. Here we demonstrate that a fine-tuned RFdiffusion network is capable of designing de novo antibody variable heavy chains (VHH’s) that bind user-specified epitopes. We experimentally confirm binders to four disease-relevant epitopes, and the cryo-EM structure of a designed VHH bound to influenza hemagglutinin is nearly identical to the design model both in the configuration of the CDR loops and the overall binding pose.
Competing Interest Statement
N.R.B., J.L.W., R.J.R., A.J.B., C.W., P.J.Y.L., B.H., and D.B. are co-inventors on U.S. provisional patent number 63/607,651 which covers the computational antibody design pipeline described here.
Footnotes
↵# Co-second author
