ABSTRACT
MOTIVATION: Molecular docking is a computational technique for predicting how a small molecule might bind a macromolecular target. Among docking programs, AutoDock Vina is particularly popular. Like many docking programs, Vina requires users to download/install an executable file and to run that file from a command-line interface. Choosing proper configuration parameters and analyzing Vina output is also sometimes challenging. These issues are particularly problematic for students and novice researchers. RESULTS: We created Webina, a new version of Vina, to address these challenges. Webina runs Vina entirely in a web browser, so users need only visit a Webina-enabled webpage. The docking calculations take place on the user's own computer rather than a remote server. AVAILABILITY AND IMPLEMENTATION: A working version of the open-source Webina app can be accessed free of charge from http://durrantlab.com/webina. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Subject(s)
Computers , Software , Humans , Ligands , Molecular Docking Simulation , Web BrowserABSTRACT
Protein structure determines biological function. Accurately conceptualizing 3D protein/ligand structures is thus vital to scientific research and education. Virtual reality (VR) enables protein visualization in stereoscopic 3D, but many VR molecular-visualization programs are expensive and challenging to use; work only on specific VR headsets; rely on complicated model-preparation software; and/or require the user to install separate programs or plugins. Here we introduce ProteinVR, a web-based application that works on various VR setups and operating systems. ProteinVR displays molecular structures within 3D environments that give useful biological context and allow users to situate themselves in 3D space. Our web-based implementation is ideal for hypothesis generation and education in research and large-classroom settings. We release ProteinVR under the open-source BSD-3-Clause license. A copy of the program is available free of charge from http://durrantlab.com/protein-vr/, and a working version can be accessed at http://durrantlab.com/pvr/.
Subject(s)
Computational Biology/methods , Imaging, Three-Dimensional/methods , Internet , Proteins , Virtual Reality , Protein Conformation , Proteins/chemistry , Proteins/ultrastructureABSTRACT
The RNA-binding protein La-related protein 1 (LARP1) plays a central role in ribosome biosynthesis. Its C-terminal DM15 region binds the 7-methylguanosine (m7G) cap and 5' terminal oligopyrimidine (TOP) motif characteristic of transcripts encoding ribosomal proteins and translation factors. Under the control of mammalian target of rapamycin complex 1 (mTORC1), LARP1 regulates translation of these transcripts. Characterizing the dynamics of DM15-TOP recognition is essential to understanding this fundamental biological process. We use molecular dynamics simulations, biophysical assays, and X-ray crystallography to reveal the mechanism of DM15 binding to TOP transcripts. Residues C-terminal to the m7G-binding site play important roles in cap recognition. Furthermore, we show that the unusually static pocket that recognizes the +1 cytosine characteristic of TOP transcripts drives binding specificity. Finally, we demonstrate that the DM15 pockets involved in TOP-specific m7GpppC-motif recognition are likely druggable. Collectively, these studies suggest unique opportunities for further pharmacological development.
