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Using Cloud Computing to Perform Molecular Dynamics Simulations of the Mutant PI3Kα Protein

10/14/2013

The lab participates in the UberCloud HPC Experiment Round 3 with the project: "TEAM 61 – Using Cloud Computing to Perform Molecular Dynamics Simulations of the Mutant PI3Kα Protein". Download the full report here.

The Ubercloud HPC Experiment aims to explore the end-to-end process of accessing remote resources in computer centers and in HPC Clouds, and to study and overcome the potential roadblocks. Read more about it from a previous blog entry.

Zoe

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How to identify the target for an active molecule?

10/11/2013

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Drug target identification, which includes many distinct algorithms for finding genes and proteins, is the first step in drug discovery. When 3D structures of the targets are available, the problem of target identification is usually converted to finding the best interaction mode between the potential target candidates and probe small molecules. But what happens when the target is unknown or we are looking for off-target effects of our active molecule? (in other words, to which other proteins does our active molecule bind?)

Three servers have been developed for this purpose:

Pharmmapper
http://59.78.96.61/pharmmapper/
PharmMapper Server is a freely accessed web-server designed to identify potential target candidates for the given probe small molecules (drugs, natural products, or other newly discovered compounds with binding targets unidentified) using pharmacophore mapping approach. Benefited from the highly efficient and robust mapping method, PharmMapper bears high throughput ability and can identify the potential target candidates from the database within a few hours.

Reversescreen3D
http://www.modelling.leeds.ac.uk/ReverseScreen3D/about.html
ReverseScreen3D is a reverse virtual screening tool that searches against a biologically-relevant and automatically-updated subset of ligands extracted from the RCSB Protein Data Bank in order to identify potential target proteins that are likely to bind a given compound.

Similarity ensemble approach (SEA)
http://sea.bkslab.org/
The Similarity ensemble approach relates proteins based on the set-wise chemical similarity among their ligands. It can be used to rapidly search large compound databases and to build cross-target similarity maps.

Read also the relevant paper:
"Target fishing and docking studies of the novel derivatives of aryl-aminopyridines with potential anticancer activity."
Bioorg Med Chem. 2012 Sep 1;20(17):5220-8. doi: 10.1016/j.bmc.2012.06.051. Epub 2012 Jul 11.Erić S, Ke S, Barata T, Solmajer T, Antić Stanković J, Juranić Z, Savić V, Zloh M.

Thanks to Mire Zloh for this information!
If you have more servers in mind, please let us know!

Zoe

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SQUEEZE-E: How to make a simulation cell based on the shape of the molecule

10/11/2013

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Read below on how the authors below made a method to define a box which is based on the shape of the molecule. This should drastically recude the number of atoms and hence simulation time! i(if the rotation is constrained)

SQUEEZE-E: The Optimal Solution for Molecular Simulations with Periodic Boundary Conditions
by Tsjerk A. Wassenaar *†‡, Sjoerd de Vries ‡, Alexandre M. J. J. Bonvin ‡, and Henk Bekker §

In molecular simulations of macromolecules, it is desirable to limit the amount of solvent in the system to avoid spending computational resources on uninteresting solvent–solvent interactions. As a consequence, periodic boundary conditions are commonly used, with a simulation box chosen as small as possible, for a given minimal distance between images. Here, we describe how such a simulation cell can be set up for ensembles, taking into account a priori available or estimable information regarding conformational flexibility. Doing so ensures that any conformation present in the input ensemble will satisfy the distance criterion during the simulation. This helps avoid periodicity artifacts due to conformational changes. The method introduces three new approaches in computational geometry: (1) The first is the derivation of an optimal packing of ensembles, for which the mathematical framework is described. (2) A new method for approximating the α-hull and the contact body for single bodies and ensembles is presented, which is orders of magnitude faster than existing routines, allowing the calculation of packings of large ensembles and/or large bodies. 3. A routine is described for searching a combination of three vectors on a discretized contact body forming a reduced base for a lattice with minimal cell volume. The new algorithms reduce the time required to calculate packings of single bodies from minutes or hours to seconds. The use and efficacy of the method is demonstrated for ensembles obtained from NMR, MD simulations, and elastic network modeling. An implementation of the method has been made available online at http://haddock.chem.uu.nl/services/SQUEEZE/ and has been made available as an option for running simulations through the weNMR GRID MD server at http://haddock.science.uu.nl/enmr/services/GROMACS/main.php.

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VMD analysis plugins for membrane simulations

10/10/2013

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MEMBPLUGIN http://sourceforge.net/p/membplugin/wiki/Home/

Diffusion Coefficient Tool http://multiscalelab.org/utilities/DiffusionCoefficientTool

VMD Density Profile Tool http://multiscalelab.org/utilities/DensityProfileTool

George

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Peptide docking with Glide

10/3/2013

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In this article, Senior Application Scientist Thijs Beuming discusses the development of a new Glide docking protocol designed specifically for peptides.

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Using Cloud Computing to Perform Molecular Dynamics Simulations of the Mutant PI3Kα Protein

How to identify the target for an active molecule?

SQUEEZE-E: How to make a simulation cell based on the shape of the molecule

VMD analysis plugins for membrane simulations

Peptide docking with Glide

Alexis, Maria, Dimitra, Ioannis, Michalis, Danai, Panos, George, Aspa, Zoe

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