Jan 18 2018
The Assign helices and Strands option will manually reassign secondary structure to a protein structure. This command does not change the geometry of the model, it only formally assigns secondary structure symbols to residues. The method uses a modification of the DSSP algorithm of automatic secondary structure assignment (Kabsch and Sander, 1983) based on the observed pattern of hydrogen bonds in a three dimensional structure. The DSSP algorithm in its original form overassigns the helical regions. For example, in the structure of T4 lysozyme (PDB code 103l ) DSSP assigns to one helix the whole region a_/93:112 which actually consists of two helices a_/93:105 and a_/108:112 forming a sharp angle of 64 degrees. ICM employs a modified algorithm which patches the above problem of the original DSSP algorithm.
To assign secondary structure:
The secondary structure sequence string (e.g. EEEEEEEEE__HHHH) will be displayed in the terminal window. Assigned secondary structure types are the following: "H" - alpha helix, "G" - 3/10 helix, "I" - pi helix, "E" - beta strand, "B" - beta-bridge, "_" or "C" - coil. If the sequence is viewed in the ICM workspace or in an alignment the secondary structure is colored as follows alpha helix (red bar), beta sheet (green bar), non-canonical helix (purple bar).
The protein health option calculates the energy strain of a structure in ICM. It is generally a good idea to investigate the energy strain of any protein structure before undertaking such processes as docking. It is also essential to use this tool after making a model (see Molecular Modeling) to identify strained regions within your model and then some optimization procedure can be undertaken to rectify the problems.
The protein health option calculates the relative energy of each residue for a selection and colors the selected residues by strain. This macro uses statistics obtained in the following paper Maiorov, V.N. and Abagyan, R.A. (1998) Energy strain in three-dimensional protein structures Folding and Design, 3 , 259-269.
To use the Protein Health option:
This option systematically samples rotamers for each residue side-chain in the input selection and uses resulting conformational ensembles to evaluate energy-weighted RMSDs for every side-chain atom. These are stored in the 'field' values on atoms and can be used for example to color the structure by side-chain flexibility. Conformational entropy for each residue side-chain is also calculated and stored in a table. If l_entropyBfactor flag is on, the atom rmsds are normalized within the residue to reflect its total conformational entropy. If l_bfactor flag is set, the bfactors are reset to the same values that are placed in the atom 'field', and occupancy is set to be inversely proportional to it ( O=1/(1+2*rmsd) )
The ICM Optimal Docking Area method is a useful way of prediciting likely protein-protein interaction interfaces. If you do not have mutational data or other experimental data which indicates the likely protein-protein docking site this method will be useful. This procedure can save you time during the docking procedure by focusing your docking only on areas on the receptor and ligand most likely to interact.
ODA (Optimal Docking Areas) is a new method to predict protein-protein interaction sites on protein surfaces. It identifies optimal surface patches with the lowest docking desolvation energy values as calculated by atomic solvation parameters (ASP) derived from octanol/water transfer experiments and adjusted for protein-protein docking. The predictor has been benchmarked on 66 non-homologous unbound structures, and the identified interactions points (top 10 ODA hot-spots) are correctly located in 70% of the cases (80% if we disregard NMR structures). For a description of the method see Fernandez-Recio et al Proteins (2005) 127: 9632.
To display the optimal docking area.
The ICM Pocket Finder method (1-2) uses only the protein structure for the prediction of cavities and clefts. No prior knowledge of the substrate is required. The position and size of the ligand-binding pocket are determined based on a transformation of the Lennard-Jones potential by convolution with a Gaussian kernel of a certain size, a grid map of a binding potential and construction of equipotential surfaces along the maps. The pockets are displayed graphically as a surface and the dimensions of each pocket are presented in an interactive table and plot.
Factors that can influence ligand binding to a pocket include the pocket volume and area, buriedness, hydrophobicity, and how compact the pocket is. All these properties are calculated using ICMPocketFinder and tabulated. Scientists at Merck used MolSoft.s ICMPocketFinder algorithm to define a way for quantifying "drugability" of a protein target (3). The metric they used is called Drug-Like-Density (DLID), and this score is also provided in the results table. A good example of the use of the icmPocketFinder method is in the database called Pocketome. The Pocketome (www.pocketome.org) is an encyclopedia of conformational ensembles of all druggable binding sites that can be identified experimentally from co-crystal structures in the Protein Data Bank (4).
1. An, J., Totrov, M. & Abagyan, R. Pocketome via comprehensive identification and classification of ligand binding envelopes. Mol. Cell. Proteomics 4, 752 (2005).
2. Abagyan, R. & Kufareva, I. The flexible pocketome engine for structural chemogenomics. Methods Mol. Biol. Clifton NJ 575, 249.279 (2009).
3. Sheridan, R. P., Maiorov, V. N., Holloway, M. K., Cornell, W. D. & Gao, Y.-D. Drug-like density: a method of quantifying the .bindability. of a protein target based on a very large set of pockets and drug-like ligands from the Protein Data Bank. J. Chem. Inf. Model. 50, 2029.2040 (2010).
4. Kufareva, I., Ilatovskiy, A. V. & Abagyan, R. Pocketome: an encyclopedia of small-molecule binding sites in 4D. Nucleic Acids Res. 40, D535.540 (2012).
To predict pockets:
About the icmPocketFinder Results Table
Factors that can influence ligand binding to a pocket include the pocket volume and area, buriedness, hydrophobicity, and how compact the pocket is. These values are reported in the results table:
|Copyright© 1989-2018, Molsoft,LLC - All Rights Reserved.|
This document contains proprietary and confidential information of
The content of this document may not be disclosed to third parties, copied or duplicated in any form,
in whole or in part, without the prior written permission from Molsoft, LLC.