Abstract. Electron cryomicroscopy is an experimental technique that is capable to produce three dimensional gray-scale images for protein molecules, called density maps. At medium resolution, the atomic details of the molecule cannot be visualized from density maps. However, some features of the molecule can be seen such as the locations of major secondary structures and the skeleton of the molecule. In addition, the order and direction of the detected secondary structure traces can be inferred. We introduce a method to construct the entire model of a protein directly for traces extracted from the density map. The initial results show that this method has good potential. A single model was built for each of the 12 proteins used in the test. The RMSD 100 of the models is slightly improved from our previous method.
Keywords:Cryo-EM · Volume image · Skeletonization · Protein modeling · Loop modeling
IntroductionElectron cryomicroscopy (cryo-EM) is an emerging technique that produces threedimensional (3D) electron density maps at a wide-range of resolutions [1][2][3][4]. When the resolution of density maps is higher than 4Å, the atomic structure can often be derived [5][6][7][8][9]. At the medium resolutions, such as 5-10Å, the backbone and the characteristic features of amino acids are not resolved. It is still challenging to derive the atomic structure from such a density map. When a component of the protein has atomic structure available, fitting can be performed to derive the atomic structure [10][11][12]. When a homologous model is available, rigid or flexible fitting can be used to derive the atomic structure [13][14][15][16][17][18]. However, it is still challenging to find a suitable template for many proteins. De novo modeling is an alternative method to derive atomic structures without relying on template structures [19][20][21][22][23][24]. It relies on the detection of secondary structure positions and the connection patterns encoded in the skeleton of the density map. A number of computational methods have been developed to detect α-helices from the density maps [25][26][27][28][29][30][31]. Most helices longer than two turns can be detected. Most of the major β-sheets can also be detected using various methods such as SheetTracer, SSEhunter,. By analyzing the twist of β-sheet