[1P-45*] gREST法によるNanobody CDR H3ループ構造のサンプリング
Single domain antibodies, known as nanobodies, are potential substitutes for conventional IgG antibodies. They have similar affinities to antigens as the conventional antibodies but are more heat-resistant. In particular, their small size allows us to exploit computational approaches for structural modeling or design. Here, we apply an enhanced sampling method, generalized replica-exchange with solute tempering (gREST) developed recently by Kamiya and Sugita (JCP, 2018), to sample nanobody CDR H3 loop structures. In the conventional replica-exchange methods, temperatures of only a whole system or molecule are exchanged to boost sampling. In gREST, we can flexibly select the temperature-exchange region as a part of a molecule or a part of the potential energy terms. Here, we define the CDR H3 loop as a temperature-exchange region and investigate which potential energy term is effective for efficient sampling of the loop structures. Using a homology-modeling structure as the initial structure, we performed gREST simulations with different potential terms for several nanobodies. The results suggest that using the dihedral-angle energy terms is the best for efficient sampling while there are some limitations depending on nanobody structures.