Aligning Structures

Maestro provides a number of ways of aligning structures so that they are in a particular orientation or so that common features are in the same spatial location. The tools that are provided contain general tools as well as tools for a specific purpose: some are designed for small molecules, others for proteins. In most cases, one of the structures is treated as a reference structure, which is not moved, and the other structures are aligned to the reference structure. Unless otherwise stated here, the reference structure is the structure that is nearest the top of the Entry List (or Project Table).

Many of the tools are available in the Task Tool under Structure Alignment.

General Alignment Tools

The tools listed below can be used on any structure. They perform rigid-body translations and rotations of the structures to align them to the target.

  • Align centers of mass—translate structures so that their centers of mass coincide. Click the Tasks button and browse to Structure Alignment → Align by Center of Mass.

  • Align to an axis or a plane—align molecules or crystal axes to one of the Cartesian axes or planes, by picking atoms to align. In the Maestro main window, choose View → Align View. For more information, see Aligning the View to the Structure.

    Align to the current view axes—change the coordinates so that the coordinate axes of the structure are the same as those of the camera view (x axis horizontal, y axis vertical, z axis out of screen). This involves a translation of the coordinate origin and a rotation. In the Maestro main window, choose Edit → Update Coordinates.

  • Rigid-body superposition—superimpose entries by rotation and translation of the structures to minimize the RMSD of a set of atoms. Clickclick the Tasks button and browse to Structure Alignment → Superposition. For more information, see the Superposition Panel topic. This panel has tools for small molecules as well as for proteins. However, application to proteins, RNA, or DNA does not take into account secondary structure—see below for other options. It is mainly useful for fairly similar structures, such as conformers, or mutants of a biopolymer, or for situations where you can specify a common substructure to superimpose.

Aligning Small Molecules

The tools for aligning small molecules include both rigid alignment and flexible alignment tools.

  • Align two molecules by specific atom correspondence—use the Superposition Panel. Pick the atoms in each of two molecules that are considered to correspond, and the RMSD of these atoms is minimized. Click the Tasks button and browse to Structure Alignment → Superposition.

  • Align molecules by a SMARTS pattern or an ASL expression—use the Superposition Panel. The SMARTS pattern can be entered or derived from the Workspace selection; the ASL expression can be entered or constructed in the Atom Selection Dialog Box. Click the Tasks button and browse to Structure Alignment → Superposition.

  • Align molecules with conformational adjustment of rotatable groups—use the Ligand Alignment Panel. The alignment can be done by shape or by common scaffold. Click the Tasks button and browse to Structure Alignment → Ligand Alignment.

  • Quick alignment of conformers—aligns all atoms in each structure in the Workspace, which must be conformers, using the Superposition tool. Click Quick Align on the Favorites toolbar or click the Tasks button and browse to Structure Alignment → Quick Align.

  • Align a set of congeneric ligands to reference ligands in a binding site—use the MCS Docking Ligand Alignment Panel. The ligands are docked with Glide to the receptor binding site, with the maximum common substructure to the reference set as a constraint. Click the Tasks button and browse to Structure Alignment → MCS Docking Ligand Alignment.

Aligning Pharmacophore Hypotheses

  • Align hypotheses to a reference hypothesis—use the Hypothesis Alignment Panel. You can find the best alignment of all features, or choose features to align on, as follows:

    To open this panel, do one of the following:

    • Click the Tasks button and browse to Ligand-Based Virtual Screening → Hypothesis Alignment
    • Click the Tasks button and browse to Structure Alignment → Hypothesis Alignment
    • Click the Tasks button and browse to Phase → Hypothesis Alignment

Aligning Proteins

Protein alignment can be done on specified parts of the protein and can take into account secondary structure.

  • Align proteins using secondary structure information—use the Protein Structure Alignment Panel. The alignment can be restricted to selected residues, and is done with a score that involves the secondary structure as well as the C-alpha RMSD. Click the Tasks button and browse to Structure Alignment → Protein Structure Alignment.

  • Align protein binding sites—use the Align Binding Sites Panel. The residues that define the binding site can be detected automatically or chosen manually; the alignment is the same as for protein alignment using secondary structure, above. Click the Tasks button and browse to Structure Alignment → Binding Site Alignment.

  • Align protein backbones—use the C-alpha tab in the Superposition Panel. The RMSD of the C-alpha atoms in residues with the same residue number is minimized. Click the Tasks button and browse to Structure Alignment → Superposition.