Dynamics of p38 MAP kinase inferred from a structural ensemble using PCA is compared to intrinsic dynamics of the protein modeled using ANM. See PCA of X-ray structures or Bioinformatics article for more details.

Workflow for comparative analysis of sequence evolution and structural dynamics is shown. See Evol Applications or Mol Biol Evol article for more details.

Results from comparative analysis of residue conservation, conformational mobility, and coevolutionary patterns for uracil-DNA glycosylase. See Mol Biol Evol article or Conservation and Coevolution Analysis for more details.

Coevolution of NEF-binding residues analzyed using mutual information is displayed for the Hsp70 ATPase domain. See PLoS Comp Biol article or Conservation and Coevolution Analysis for details.

Comparative analysis of p38 MAP kinase dynamics from experiments (PCA) and theory (ANM). See the PNAS article or figure for details.

Comparative analysis of dynamics of drug target proteins and model systems from experiments (PCA) and theory (ANM). See the Protein Science article for details.

Comparative analysis of p38 MAP kinase dynamics from experiments (PCA), simulations (EDA), and theory (ANM). See the Protein Science article for details.

Animation shows HIV-1 reverse transcriptase functional motions calculated using anisotropic network model. Arrows and animations are generated using NMWiz VMD plugin. See NMWiz tutorial for usage examples.

You can make a quick protein representation in interactive sessions using showProtein() function.

NMWiz is designed for picturing normal modes easy. Image shows arrows from slowest three ANM modes for p38 MAP kinase centered at the origin. They indeed align with planes normal to each other.

NMWiz makes depicting elastic network models and protein motions predicted with them easy. Image shows ANM model for p38 MAP kinase and three slow ANM modes (below).

NMWiz can be used to comparative dynamics inferred from experimental datasets and predicted using theory.

The movie shows a molecular dynamics simulation for assessing the druggability of kinesin eg5. NMWiz VMD plugin. See NMWiz tutorial for usage examples.

Kinesin Eg5 druggable sites, including allosteric inhibitor binding site and and tubulin binding site, identified by simulations are shown. See our publication for details.

Sampling of the functional substates (inward-facing (IF) or outward-facing (OF), in closed (c) or open (o) forms) of LeuT using coMD simulations. See publication for details.

The movie illustrates a coMD trajectory for adenylate kinase. NMWiz VMD plugin. See NMWiz tutorial for usage examples.

Energy landscape in the space of principal coordinates.

Outward-facing (OF) and inward-facing (IF) structures of GltPh show a large displacement of the core domains. See publication for details.

The second mode of the OF structure moves all three transport domains simultaneously through the membrane in a ‘lift-like’ motion. See publication for details.

The second mode of the IF structure moves all three transport domains simultaneously through the membrane in a ‘lift-like’ motion. See publication for details.

Deformability profile of ubiquitin (PDB code: 1UBI). Structure is automatically uploaded to VMD program where blue color shows regions which are mechanically more resistant to the external force.

Mean value of effective spring constant (calculated from mechanical stiffness matrix) with secondary structure of ubiquitin. Blue color indicates mechanically strong regions.

Mechanical Stiffness Map with effective force constant in a color bar (blue - strong regions, red - weak regions) for ubiquitin.

Workflow for GNM analysis of chromatin dynamics. See publication for details.

Covariance matrix of chromosome 17 of human B cells. Structural domains and CCDDs are identified and outlined. See publication for details.

3D Laplacian embedding of chromosome 17 loci using the first three principal modes. See ChromD tutorial for details.

Perturbation response scanning of the Hsp70 chaperone reveals interdomain allostery. See publication for details.

Perturbation response scanning of the AMPA-type glutamate receptor reveals sensors and effectors for allosteric signaling. See publication for details.

A more in-depth analysis of the PRS matrix reveals interdomain signaling in the AMPA receptor. See publication for details.

The left panels show the three softest GNM modes (blue lines) and their standard deviations (faint blue bands). Red and blue regions in the corresponding ribbon diagrams show regions moving in opposite directions. The right panel has the average cross-correlation matrix from the first 20 global modes (top) and its standard deviation (bottom).

Square fluctuations calculated from the top 5 global modes are shown for a number of LeuT fold family members, revealing similarities and subfamily- or conformation-dependent differences.

Type-I periplasmic binding protein domains are mapped onto the first two signature ANM modes. These domains, found in a range of proteins including bacterial solute carriers and eukaryotic receptors, have two lobes that undergo well-characterised conserved motions that are evident from comparison of structures. SignDy reveals such conserved dynamics.

SignDy analysis allows a comparison of the frequency dispersion of family members. The distribution of inverse eigenvalues is shown for the softest five modes for TIM barrel fold family.

PRS for Perturbation Response Scanning

PRS calculates the effectiveness and sensitivity of residues in propagating allosteric signals.

Features

PRS uses as input the known structure modeled as an elastic network (ANM). It is used to evaluate how spatial perturbation of residue i affects the dynamics of residue j, shown in a PRS map. The row and column averages of the PRS map describe effectiveness and sensitivity profiles of residues. The output can be used for identification of:

  1. effector residues that most efficiently propagate signals in response to external perturbations
  2. sensor residues that have a high propensity to sense signals and respond with altered dynamics
  3. important connections for signaling within a protein
Reference
Dutta A, Krieger J, Lee JY, Garcia-Nafria J, Greger IH, Bahar I. Cooperative Dynamics of Intact AMPA and NMDA Glutamate Receptors: Similarities and Subfamily-Specific Differences. Structure 2015 23(9):1692-1704.
General IJ, Liu Y, Blackburn ME, Mao W, Gierasch LM, Bahar I. ATPase subdomain IA is a mediator of interdomain allostery in Hsp70 molecular chaperones. PLoS Comput Biol 2014 10(5):e1003624.
Atilgan C, Atilgan AR. Perturbation-response scanning reveals ligand entry-exit mechanisms of ferric binding protein. PLoS Comput Biol 2009 5(10):e1000544.

People

ProDy is developed in Bahar Lab at the University of Pittsburgh. Click here to see a list of people who contributed to its development.

Community

ProDy makes use of great open source software including NumPy, Pyparsing, Biopython, SciPy, and Matplotlib. Click here for details.

Source Code

ProDy is open source and you can contribute to its development in many ways. See this guide for getting started.

Problems?

Let us know any problems you might have by opening an issue at the tracker so that we can make ProDy better.