UMMS: constrained harmonic and anharmonic analyses of macromolecules based on elastic network models

Abstract

UMass Morph Server (UMMS) has been developed for the broad impact on the study of molecular dynamics (MD). The elastic network model (ENM) of a given macromolecule has been proven as a useful tool for analyzing thermal behaviors locally and predicting folding pathways globally. UMMS utilizes coarse-grained ENMs at various levels. These simplifications remarkably save computation time compared with all-atom MD simulations so that one can bring down massive computational problems from a supercomputer to a PC. To improve computational efficiency and physical reality of ENMs, the symmetry-constrained, rigid-cluster, hybrid and chemical-bond ENMs have been developed and implemented at UMMS. One can request both harmonic normal mode analysis of a single macromolecule and anharmonic pathway generation between two conformations of a same molecule using elastic network interpolation at http://biomechanics.ecs.umass.edu/umms.html.

Figure 1

Schematic representation of the working procedure of UMMS. Harmonic NMA and anharmonic pathway generation can be performed based on user's requests. The default setting of coarse-graining method for protein is to take only alpha-carbon atoms per residue. Its resolution is probably enough to investigate the global dynamics of proteins in most of cases. For small proteins (approximately <1000 atoms), backbone-trace ENMs including only heavy atoms along the protein backbone and full-atom ENMs are also practicable in a PC. Regardless of the level of coarse-graining of ENMs, a single-parameter Hookean potential is defined in Cartesian space and then differentiated resulting in the stiffness matrix for NMA. MD data interpretation and incorporation with experimental data such as FRET and NMR are also available at UMMS. For more details, see the section of applications.

Figure 2

Overview of UMMS. The main page (middle panel) consists of NMA database, ENI database and query windows. One can not only browse NMA or ENI database to access the existing result of a specific macromolecule of interest, but also request the analysis via the query windows. A typical NMA window (upper left panels) shows animated mode shapes with various representations, the connectivity map of ENM called linking matrix, and the B-factor comparison plot. An ENI window (upper right panels) presents the computed ENI pathway between the two end conformations. One can download both animations and data files (PDB and text format) from those windows. Four different query windows (lower panels) are used for submitting the structural information of macromolecules (PDB ID, Cartesian coordinate file, MD trajectory data, FRET distance data) and choosing the simulation parameters (coarse-graining method, cutoff rule, output representation type).