Analyzing Residue Surface Proximity to Interpret Molecular Dynamics

Abstract

Figure 1: From an input molecule (left), we derive a surface proximity term (center, left) that represents the closeness of an atom to the molecule surface. We apply this method to a Molecular Dynamics simulation to obtain a color-coded map, representing the trajectory for each atom or residue (center). Single time-steps can be visualized in 3D (right), e.g., VdW-spheres or in a combined backbone-helix form. AbstractThe surface of a molecule holds important information about the interaction behavior with other molecules. In dynamic folding or docking processes, residues of amino acids with different properties change their position within the molecule over time. The atoms of the residues that are accessible to the solvent can directly contribute to binding interactions, while residues buried within the molecular structure contribute to the stability of the molecule. Understanding patterns and causality of structural changes is important for experts in the pharmaceutical domain, e.g., in the process of drug design. We apply an iterative computation of the Solvent Accessible Surface in order to extract virtual layers of a molecule. The extraction allows to track the movement of residues in the body of the molecule, with respect to the distance of the residue to the surface or the core during dynamics simulations. We visualize the obtained layer information for the complete time span of the molecular dynamics simulation as a 2D-map and for individual time-steps as a 3D-representation of the molecule. The data acquisition has been implemented alongside with further analysis functionality in a prototypical application, which is available to the public domain. We underline the feasibility of our approach with a study from the pharmaceutical domain, where our approach has been used for novel insights into the folding behavior of µ-conotoxins.

Scale-Space Splatting: Reforming Spacetime for Cross-Scale Exploration of Integral Measures in Molecular Dynamics

“…Lichtenberg et al [29] present a visual analytics tool for exploring molecular structures based on the Solvent Accessible Surface (SAS). This is a geometric approach to the extraction of the spatial configuration of a protein-ligand interaction.…”