Introduction

This tutorial demonstrates how to use perturbation response scanning (PRS) to determine sensors and effectors, which are important for allosteric signal transduction. The PRS approach is derived from linear response theory where perturbation forces are applied via a covariance matrix, which can be derived from elastic network models or MD simulations.

The example used in this tutorial is the AMPA-type ionotropic glutamate receptor (AMPAR; PDB 3kg2), which we studied using this method (see Figure 6 of [AD15]).

The theory was originally described in [CA09] and [CA10], and extended to include sensors in [IG14].

Required Programs

The latest version of ProDy is recommended along with NumPy and Matplotlib. IPython is highly recommended for interactive usage.

Getting Started

To follow this tutorial, you will not need any additional files.

We recommend that you will follow this tutorial by typing commands in an IPython session, e.g.:

$ ipython

or with pylab environment:

$ ipython --pylab

First, we will make necessary imports from ProDy and Matplotlib packages.

In [1]: from prody import *

In [2]: from pylab import *

In [3]: ion()

We have included these imports in every part of the tutorial, so that code copied from the online pages is complete. You do not need to repeat imports in the same Python session.

How to Cite

If you benefited from Perturbation Response Analysis in your research, please cite the following papers:

[CA09]

Atilgan C, Atilgan AR. Perturbation-response scanning reveals ligand entry-exit mechanisms of ferric binding protein. PLoS Comput. Biol. 2009 5:e1000544.

[CA10]

Atilgan C, Gerek ZN, Ozkan SB, Atilgan AR. Manipulation of conformational change in proteins by single-residue perturbations. Biophys. J. 2010 99(3):933-43

[IG14]

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:e1003624.

[AD15]

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 23:1692-1704