iMODS: internal coordinates normal mode analysis server

Abstract

Normal mode analysis (NMA) in internal (dihedral) coordinates naturally reproduces the collective functional motions of biological macromolecules. iMODS facilitates the exploration of such modes and generates feasible transition pathways between two homologous structures, even with large macromolecules. The distinctive internal coordinate formulation improves the efficiency of NMA and extends its applicability while implicitly maintaining stereochemistry. Vibrational analysis, motion animations and morphing trajectories can be easily carried out at different resolution scales almost interactively. The server is versatile; non-specialists can rapidly characterize potential conformational changes, whereas advanced users can customize the model resolution with multiple coarse-grained atomic representations and elastic network potentials. iMODS supports advanced visualization capabilities for illustrating collective motions, including an improved affine-model-based arrow representation of domain dynamics. The generated all-heavy-atoms conformations can be used to introduce flexibility for more advanced modeling or sampling strategies. The server is free and open to all users with no login requirement at http://imods.chaconlab.org.

Figure 1.

Screenshot of iMODS results obtained from the Ca²⁺-ATPase structure. The center frame displays the functional domain motions encoded by the lowest-frequency mode. The actuator (A), phosphorylation (P), nucleotidic (N) and transmembrane (M) functional domains appear in red, cyan, green and yellow, respectively. The arrows obtained with the affine-model-based approach are colored accordingly.

Figure 2.

NMA of GroEL/ES complex. Affine model clusters computed from a single trans GroEL monomer (A). The characterized dynamical domains in yellow, cyan and red are in agreement with the apical, intermediate and equatorial functional domains, respectively. The GroEL monomer structure is colored as a function of deformability (B) and mobility (C). The GroEL/ES deformability (D) and mobility (E) were calculated from the NMA of the whole complex.

Figure 3.

GroEL monomer cis/trans transition. The trajectory of the large conformational change between the open (cis) and closed (trans) structures. Initial (left) and final (right) conformations are illustrated superimposed with the target structure in grey. Notice how the Cα-RMSD between the trajectory models and the target structure smoothly converges to ∼1 Å. All-heavy-atoms were considered, including the ATP/Mg²⁺ ligand. All of the figures were generated from images provided by iMODS.