LAUSR

Formins accelerate actin polymerization, assumed to occur through flexible Formin Homology 1 (FH1) domain‐mediated transfer of profilin‐actin to the barbed end. To study FH1 properties and address sequence effects, including varying length/distribution of profilin‐binding proline‐rich motifs, we performed all‐atom simulations of a set of representative FH1 domains of formins: mouse mDia1 and mDia2, budding yeast Bni1 and Bnr1, and fission yeast Cdc12, For3, and Fus1. We find FH1 has flexible regions between high‐propensity polyproline helix regions. A coarse‐grained model retaining sequence specificity, assuming rigid polyproline segments, describes their size. Multiple bound profilins or profilin‐actin complexes expand mDia1‐FH1, which may be important in cells. Simulations of the barbed end bound to Bni1‐FH1‐FH2 dimer show that the leading FH1 can better transfer profilin or profilin‐actin, with decreasing probability as the distance from FH2 increases.