Article

M-ZDOCK: a grid-based approach for C-n symmetric multimer docking

Bioinformatics Program, Boston University, Boston, MA, USA.
Bioinformatics (Impact Factor: 4.62). 05/2005; 21(8):1472-8. DOI: 10.1093/bioinformatics/bti229
Source: PubMed

ABSTRACT Computational protein docking is a useful technique for gaining insights into protein interactions. We have developed an algorithm M-ZDOCK for predicting the structure of cyclically symmetric (Cn) multimers based on the structure of an unbound (or partially bound) monomer. Using a grid-based Fast Fourier Transform approach, a space of exclusively symmetric multimers is searched for the best structure. This leads to improvements both in accuracy and running time over the alternative, which is to run a binary docking program ZDOCK and filter the results for near-symmetry. The accuracy is improved because fewer false positives are considered in the search, thus hits are not as easily overlooked. By searching four instead of six degrees of freedom, the required amount of computation is reduced. This program has been tested on several known multimer complexes from the Protein DataBank, including four unbound multimers: three trimers and a pentamer. For all of these cases, M-ZDOCK was able to find at least one hit, whereas only two of the four testcases had hits when using ZDOCK and a symmetry filter. In addition, the running times are 30-40% faster for M-ZDOCK. AVAILABILITY: M-ZDOCK is freely available to academic users at http://zlab.bu.edu/m-zdock/ CONTACT: zhiping@bu.edu SUPPLEMENTARY INFORMATION: http://zlab.bu.edu/m-zdock.

0 Followers
 · 
135 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mitochondrial calcium uniporter (MCU) channel is responsible for Ruthenium Red-sensitive mitochondrial calcium uptake. Here, we demonstrate MCU oligomerization by immunoprecipitation and Förster resonance energy transfer (FRET) and characterize a novel protein (MCUb) with two predicted transmembrane domains, 50% sequence similarity and a different expression profile from MCU. Based on computational modelling, MCUb includes critical amino-acid substitutions in the pore region and indeed MCUb does not form a calcium-permeable channel in planar lipid bilayers. In HeLa cells, MCUb is inserted into the oligomer and exerts a dominant-negative effect, reducing the [Ca(2+)]mt increases evoked by agonist stimulation. Accordingly, in vitro co-expression of MCUb with MCU drastically reduces the probability of observing channel activity in planar lipid bilayer experiments. These data unveil the structural complexity of MCU and demonstrate a novel regulatory mechanism, based on the inclusion of dominant-negative subunits in a multimeric channel, that underlies the fine control of the physiologically and pathologically relevant process of mitochondrial calcium homeostasis.
    The EMBO Journal 07/2013; DOI:10.1038/emboj.2013.157 · 10.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Protein-Protein docking is a recent practice in biological research which involves using 3D models of proteins to predict the structure of complexes formed by these proteins. Studying protein-protein interactions and how proteins form molecular complexes allows researchers to better understand their function in the cell. Currently, the most common methods used for docking are fully computational approaches, followed by the use of molecular visualization tools to evaluate results. However, these approaches are time consuming and provide a large number of potential solutions. Our basic hypothesis is that a virtual reality (VR) framework for molecular docking can combine the benefits of multimodal rendering, of the biologist's expertise in the field of docking, and of automated docking algorithms. We think this approach will increase efficiency in reaching the solution of a docking problem. However designing immersive and multimodal virtual environments (VE) based on VR technology calls for clear and early identification of user needs. To this end, we have analyzed the task of protein-protein docking as it is carried out today, in order to identify benefits and shortcomings of existing tools, and support the design of new interactive paradigms. Using these results, we have defined a new approach and designed a multimodal application for molecular docking in a virtual reality context.
    3D User Interfaces, 2008 IEEE Symposium on; 04/2008
  • Source

Preview

Download
3 Downloads
Available from