SUMMARY: CrocoBLAST is a tool for dramatically speeding up BLAST+ execution on any computer. Alignments that would take days or weeks with NCBI BLAST+ can be run overnight with CrocoBLAST. Additionally, CrocoBLAST provides features critical for NGS data analysis, including: results identical to those of BLAST+; compatibility with any BLAST+ version; real-time information regarding calculation progress and remaining run time; access to partial alignment results; queueing, pausing, and resuming BLAST+ calculations without information loss. AVAILABILITY AND IMPLEMENTATION: CrocoBLAST is freely available online, with ample documentation (webchem.ncbr.muni.cz/Platform/App/CrocoBLAST). No installation or user registration is required. CrocoBLAST is implemented in C, while the graphical user interface is implemented in Java. CrocoBLAST is supported under Linux and Windows, and can be run under Mac OS X in a Linux virtual machine. CONTACT: [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The pro-apoptotic proteins Bax and Bak are essential for executing programmed cell death (apoptosis), yet the mechanism of their activation is not properly understood at the structural level. For the first time in cell death research, we calculated intra-protein charge transfer in order to study the structural alterations and their functional consequences during Bax activation. Using an electronegativity equalization model, we investigated the changes in the Bax charge profile upon activation by a functional peptide of its natural activator protein, Bim. We found that charge reorganizations upon activator binding mediate the exposure of the functional sites of Bax, rendering Bax active. The affinity of the Bax C-domain for its binding groove is decreased due to the Arg94-mediated abrogation of the Ser184-Asp98 interaction. We further identified a network of charge reorganizations that confirms previous speculations of allosteric sensing, whereby the activation information is conveyed from the activation site, through the hydrophobic core of Bax, to the well-distanced functional sites of Bax. The network was mediated by a hub of three residues on helix 5 of the hydrophobic core of Bax. Sequence and structural alignment revealed that this hub was conserved in the Bak amino acid sequence, and in the 3D structure of folded Bak. Our results suggest that allostery mediated by charge transfer is responsible for the activation of both Bax and Bak, and that this might be a prototypical mechanism for a fast activation of proteins during signal transduction. Our method can be applied to any protein or protein complex in order to map the progress of allosteric changes through the proteins' structure.