Protein dynamics can be used as filtering criteria for the design of highly selective small molecules

Summary

Protein dynamics can be used as filtering criteria when designing highly selective small molecules (1). MD simulations showed how dynamics differ in two closely targets, FGFR1 and FGFR2, leading to the design of small molecules that preferred the more ordered substructures of the latter.

Figures

Ref (1)

See also

• Modifying conformational landscapes of proteins can give rise to new functions

1.

Schönherr H, Ayaz P, Taylor AM, Casaletto JB, Touré BB, Moustakas DT, et al. Discovery of lirafugratinib (RLY-4008), a highly selective irreversible small-molecule inhibitor of FGFR2. Proceedings of the National Academy of Sciences. 2024;121(6). Available from: https://doi.org/10.1073/pnas.2317756121