February 2009

Accelrys Discovery Studio Newsletter

News and Information

• Final signup opportunity for the Accelrys User Group meeting February 18-20th! Full details are here.
• Life Sciences Product training: Accelrys training offerings are available here.
  

Tips & Tricks

Simple Superimpositions using the Toolbar

Simple superimpositions of two molecules can be performed using the Tether tool. This done by selecting at least three pairs of "tethers" then superimposing . To make this easier display the Alignment toolbar (View/Toolbars/Alignment). Select two atoms, one from each molecule then click the "Add Tether" tool in the Alignment tool bar. The order of selection is not important. The second molecule loaded is always superimposed on the first.

Repeat this at least twice more to define at least 3 tethers total. To superimpose the molecules based on the defined tethers click on the "Superimpose by Tether" option in the Alignment toolbar.

Featured Journal Article

Optimization of Electrostatic Interactions in Protein-Protein Complexes

ABSTRACT: In this article, we present a statistical analysis of the electrostatic properties of 298 protein-protein complexes and 356 domain-domain structures extracted from the previously developed database of protein complexes (ProtCom, http://www.ces.clemson.edu/compbio/protcom). For each structure in the dataset we calculated the total electrostatic energy of the binding and its two components, Coulombic and reaction field energy. It was found that in a vast majority of the cases (.90%), the total electrostatic component of the binding energy was unfavorable. At the same time, the Coulombic component of the binding energy was found to favor the complex formation while the reaction field component of the binding energy opposed the binding. It was also demonstrated that the components in a wild-type (WT) structure are optimized/anti-optimized with respect to the corresponding distributions, arising from random shuffling of the charged side chains. The degree of this optimization was assessed through the Z-score of WT energy in respect to the random distribution. It was found that the Z-scores of Coulombic interactions peak at a considerably negative value for all 654 cases considered while the Z-score of the reaction field energy varied among different types of complexes. All these findings indicate that the Coulombic interactions within WT protein-protein complexes are optimized to favor the complex formation while the total electrostatic energy predominantly opposes the binding. This observation was used to discriminate WT structures among sets of structural decoys and showed that the electrostatic component of the binding energy is not a good discriminator of the WT; while, Coulombic or reaction field energies perform better depending upon the decoy set used.

Kelly Brock, et al., Biophysical Journal Volume 93 November 2007 3340–3352, Optimization of Electrostatic Interactions in Protein-Protein Complexes

Community Forum Highlight

PrepareProtein (Auto Complete)

The PrepareProtein protocol cleans up common problem in input protein structures in preparation for their use in other protocols, for example the Simulation protocols.
(1)Standardize atom names, insert missing atoms in residues and remove alternate conformations
(2) Insert Missing Loop Regions based on SEQRES data
(3) Optimize Short and Medium Size Loop Regions with Looper Algorithm
(4) Minimize Remaining Loop Regions
(5) Calculate pK and Protonate Structure

Note: In order make use of all steps listed above, this protocol requires MODELLER, Biopolymer, Protein Refinement and CHARMm or CHARMm Lite licenses.

This protocol can be downloaded here.

Protocol of the Month

Analysis of ZDOCK poses: Calculate Contact Surface Area

The quality of a protein- protein docked poses is often correlated with increasing contact surface area.

This script processes "Dock Proteins (ZDock)" poses and calculates the contact surface area between the receptor and ligand proteins. The contact surface area is calculated as the change in the solvent accessible surface (SAS) area values upon formation of receptor-ligand protein complex:
<Contact SA> = <SAS of Receptor protein alone> + <SAS of Ligand protein alone> - <SAS of docked protein complex>
The Contact SA is added as a new property in the ProteinPose tab of the input ZDock data and the values are also reported in the standard output which can be copied and pasted into a spreadsheet program.

The script can be accessed from our forums page here.