Many spherical viruses and some enzyme complexes form particles having icosahedral symmetry. The use of electron cryomicroscopy and single particle reconstruction has allowed us to visualize the 3-dimensional structures of this type of particle to 7-9 A resolution. This resolution is sufficient to resolve long alpha helices and recognize large beta sheets. In the past three years, we have determined 6 structures of icosahedral particles with sizes ranging from 600 -1250 A in this resolution range. They include herpesvirus capsid, rice dwarf virus, procapsid and mature forms of P22 bacteriophage, rotavirus and cytoplasmic polyhedrosis virus. With this experience, we have identified a number of possible improvements in the suite of software specific to the icosahedral particle reconstruction in order to improve the ease of its future maintenance and upgrade, the accuracy of determined structure, the ease of usage by biology end-users and the computational efficiency. In this proposal, we will have four specific goals.
The first aim i s to rewrite the major codes in C++, which includes the icosahedral particle center and orientation refinement and the Fourier Bessel reconstruction. They will be optimized for both shared and distributed computer platforms and will be written in modular form to make them easy to maintain and modify.
The second aim i s to improve the algorithms for particle orientation parameter refinement, contrast transfer function and B factor corrections and Fourier Bessel reconstruction respectively. We expect that these improved codes will lead to a more accurate structure determination of icosahedral particles.
The third aim i s to integrate the improved codes with a Python language binder together with a user-friendly graphical interface and to output relevant intermediate data processing results that would allow the users to decide if the refinement is heading to the correct structure convergence.
The fourth aim i s to document the codes adequately with a help menu and to disseminate them broadly and freely through the internet access. Before the software release, we will confirm their reliability and accuracy by testing with simulated and experimental data. The experimental data consist of structures that we have previously determined to subnanometer resolution and for which the crystal structures of some of their components are known.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-SSS-H (91))
Program Officer
Deatherage, James F
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor College of Medicine
Schools of Medicine
United States
Zip Code
Yang, C; Jiang, W; Chen, D-H et al. (2009) Estimating contrast transfer function and associated parameters by constrained non-linear optimization. J Microsc 233:391-403
Liu, Xiangan; Jiang, Wen; Jakana, Joanita et al. (2007) Averaging tens to hundreds of icosahedral particle images to resolve protein secondary structure elements using a Multi-Path Simulated Annealing optimization algorithm. J Struct Biol 160:11-27
Jiang, Wen; Chiu, Wah (2007) Cryoelectron microscopy of icosahedral virus particles. Methods Mol Biol 369:345-63
Jiang, Wen; Chang, Juan; Jakana, Joanita et al. (2006) Structure of epsilon15 bacteriophage reveals genome organization and DNA packaging/injection apparatus. Nature 439:612-6
Chang, Juan; Weigele, Peter; King, Jonathan et al. (2006) Cryo-EM asymmetric reconstruction of bacteriophage P22 reveals organization of its DNA packaging and infecting machinery. Structure 14:1073-82
Chiu, Wah; Baker, Matthew L; Jiang, Wen et al. (2005) Electron cryomicroscopy of biological machines at subnanometer resolution. Structure 13:363-72
Cong, Yao; Jiang, Wen; Birmanns, Stefan et al. (2005) Fast rotational matching of single-particle images. J Struct Biol 152:104-12