Glossary of ProDy Terminology

ProDy Terminology (core)

This page provides you a simpler explanation/reminder for the terminology commonly used in ProDy.

ProDy Terminology	Description
Elastic Network Model (ENM)	The ENM represents a given protein or a protein complex by a network of nodes (or to say, beads) connected by elastic springs. For example, if a protein is composed of N residues, the ENM represents this protein as an elastic network composed of N nodes, positioned at α-carbon of each residue, and elastic springs of uniform force constant connecting residue pairs within a cutoff distance (e.g., 10 Å). ENM is especially useful to study large molecular machines. These molecular machineries often undergo collective conformational transitions and such motions are at long timescales, which are beyond the capability of sampling using full atomic simulations. There are two ENMs, Gaussian Network Model (GNM) and Anisotropic Network Model (ANM), which are our main focus.
Gaussian Network Model (GNM)	In GNM, each node, $i$, is subject to Gaussian fluctuations $\Delta R_i$ about their mean position (e.g., positions determined by X-ray). Inter-residue distances, $R_{ij}$, also undergo Gaussian fluctuations, with the expression $\Delta R_{ij}=\Delta R_j-\Delta R_i$. GNM has mode shapes in N-dimensional space, and the connectivity of GNM (i.e. the residue $i$ is in contact with k number of residues within the cutoff distance) is defined by the Kirchhoff matrix, $\Gamma$. GNM is an isotropic network model, which means the mean square fluctuations along the x, y and z-direction is the same, with the expression $<(\Delta x_i)^2>=<(\Delta y_i)^2>=<(\Delta z_i)^2>$. So, $<(\Delta R_i)^2>=<(\Delta x_i)^2>+<(\Delta y_i)^2>+<(\Delta z_i)^2>=3<(\Delta x_i)^2>$. Hence there is no information on the ‘directions’ of motions in different modes, but just their sizes.
Anisotropic Network Model (ANM)	In order to assess the directions of motions, an extension of GNM called Anisotropic Network Model (ANM) has been introduced. Instead of using $\Delta R_i$ to represent fluctuations, $\Delta R_i=(\Delta x_i, \Delta y_i, \Delta z_i)^T$. Thus, ANM is 3N-dimentional. As such, each element in the NxN Kirchhoff matrix of GNM is converted into a 3x3 supper element, which is the Hessian.
Kirchhoff Matrix	Kirchhoff matrix, $\Gamma$, (an NxN matrix) defines the connectivity of the GNM.
Hessian Matrix	Hessian matrix, H, (a 3Nx3N matrix) defines the connectivity of the ANM.

ProDy Terminology (additional)

ProDy Terminology (additional)	Description
Essential Site Scanning Analysis (ESSA)	ESSA identifies the residues whose perturbation upon ligand binding would cause a significant change in the frequency dispersion of global modes. These residues are called essential residues, as they play a dominant role in controlling the proteins’ essential dynamics. Perturbations are serially made on each residue via insertion of new nodes located at the heavy atoms of their sidechains for mimicking the crowding/constraints in their local environment imparted by ligand binding. The mean shift (usually increase) induced in the frequency of the softest modes is used as a measure of essentiality. Essential residues may include those participating in allosteric and orthosteric sites, as well as those modulating global hinge bending movements.
ClustENMD	ClustENMD is a hybrid method that performs unbiased conformational sampling of highly flexible and/or large biomolecular systems. ClustENMD combines ENM and molecular dynamics (MD) simulations for conformational samplings. There are three major iterative steps in a ClustENMD simulation: 1) deforming each conformer (from previous generation) along random combinations of global ANM modes for generating new conformers; 2) clustering of new conformers to find cluster representative; and 3) performing a short MD simulation for each cluster representative using OpenMM software.