[3P-1] Poster 3 (3P-01ー3P-47)

[3P-34] Efficient flexible fitting refinement for de novo structure modeling from cryo-EM density maps

^○Takaharu Mori¹, Genki Terashi², Daisuke Matsuoka¹, Daisuke Kihara², Yuji Sugita^1,3,4 (1.RIKEN CPR, 2.Purdue University, 3.RIKEN BDR, 4.RIKEN R-CCS)

Structural modeling of proteins from cryo-EM density maps is one of the challenging issues in structural biology. De novo modeling combined with flexible fitting refinement (FFR) has been widely used to build a structure of new proteins. In de novo prediction, artificial conformations containing local structural errors such as chirality errors, cis peptide bonds, and ring penetrations are frequently generated and cannot be easily removed in the subsequent FFR. Moreover, refinement can be significantly suppressed due to the low mobility of atoms inside the protein. To overcome these problems, we propose an efficient scheme for FFR, in which the local structural errors are fixed first, followed by FFR using an iterative simulated annealing (SA) molecular dynamics (MD) protocol with the united atom (UA) model in an implicit solvent model; we call this scheme "SAUA-FFR". The SAUA-FFR scheme realizes efficient and accurate protein structure modeling from medium-resolution maps with less overfitting.