Minimize Structure

Minimize Structure energy-minimizes molecule models, optionally holding some atoms fixed. Minimization routines are provided by MMTK, which is included with Chimera. Amber parameters are used for standard residues, and Amber's Antechamber module (also included with Chimera) is used to assign parameters to nonstandard residues.

Minimize Structure is in development and has several limitations. It is intended for cleaning up small molecule structures and improving localized interactions within larger systems. It may not be able to resolve large-scale distortions or widespread structural problems. By definition, energy-minimization simply moves the system toward a local minimimum without crossing energy barriers, and does not search for the global minimum.

There are several ways to start Minimize Structure, a tool in the Structure Editing category. It is also implemented as the command minimize.

Models to minimize can be chosen from the list with the left mouse button. Ctrl-click toggles the status of an individual model. To choose a block of models without dragging, click on the first (or last) and then Shift-click on the last (or first) in the desired block. All chosen models are treated as a single system for energy calculations; other models are ignored. Within the chosen models, all atoms are included in energy calculations, regardless of whether they are held fixed. (However, parts of models can be excluded from energy calculations using the minimize command with fragment true.)

Steepest descent minimization is performed first to relieve highly unfavorable clashes, followed by conjugate gradient minimization, which is much slower but more effective at reaching an energy minimum after severe clashes have been relieved. Energies (kJ/mol) are reported in the Reply Log. **Step numbers reported by MMTK are 2 greater than the actual numbers of minimization steps performed. The additional “steps” are not minimization steps but operations required to obtain gradient values and updated coordinates.**

• Steepest descent steps (default 100) - number of steps of steepest descent minimization to perform before any conjugate gradient minimization
• Steepest descent step size (Å) (default 0.02) - initial step length for steepest descent minimization
• Conjugate gradient steps (default 10) - number of steps of conjugate gradient minimization to perform after finishing any steepest descent minimization
• Conjugate gradient step size (Å) (default 0.02) - initial step length for conjugate gradient minimization
• Update interval (default 10) - how frequently to update the display, in terms of minimization steps
• Fixed atoms - atoms to hold in place during minimization:
  • none (default) - all atoms will be allowed to move
  • selected - any selected atoms should be held fixed, all other atoms allowed to move
  • unselected - any selected atoms should be allowed to move, all other atoms held fixed
• Memorize options chosen in subsequent dialogs - as explained below, Dock Prep and further tools may be called to prepare structures for minimization; this option specifies saving their settings in the preferences file for future uses of Minimize Structure
• Use previously memorized options, if any - use settings saved with the preceding option in a prior use of Minimize Structure
• Neither memorize nor use memorized options - do not use previously saved settings; show the dialogs so that settings can be chosen explicitly for this use of Minimize Structure, but do not save the settings

• AddH to add hydrogens. If Minimize has already been clicked, the selection will be adjusted prior to minimization to include any newly attached atoms in the fixed and movable sets. Note that any other models in the vicinity will influence hydrogen placement even if hydrogens are not being added to those other models. If such interactions are not desired, the other models should be closed beforehand.
  
  
• Add Charge to associate atoms with partial charges and other force field parameters. Required even when alternative charges will be used.

• adding hydrogens separately beforehand allows them to be deleted or repositioned as needed prior to minimization
• adding charges separately beforehand allows alternative charges to be specified prior to minimization

Different procedures are used to assign parameters to standard residues, monatomic ions, and nonstandard residues.

Standard residues include water, standard amino acids, standard nucleic acids, and a few common variants and capping groups.

1. Add Charge recognizes standard residues based on their atom and residue names and assigns Amber residue names, Amber atom types, and atomic partial charges from an Amber force field chosen by the user, default ff12SB (details).
2. Minimize Structure uses the Amber atom types to associate the atoms with other parameters from the chosen force field.

Nonstandard residues are all residues not recognized as standard residues or monatomic ions.

1. Add Charge uses Amber's Antechamber module (included with Chimera) to assign GAFF types and calculate atomic partial charges within each nonstandard residue. It is necessary to specify the formal charge of each nonstandard residue and which charge calculation method should be used. Publications involving Antechamber use should cite:

   Automatic atom type and bond type perception in molecular mechanical calculations. Wang J, Wang W, Kollman PA, Case DA. J Mol Graph Model. 2006 Oct;25(2):247-60.

   Note that Antechamber/GAFF are meant to handle most small organic molecules, but not metal complexes, inorganic compounds, or unstable species such as radicals, and may not work well on highly charged molecules.
   
   
2. Minimize Structure uses the GAFF types to associate nonstandard residues with parameters other than charges. The GAFF atom types and associated parameters are described online and in:

   Development and testing of a general amber force field. Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA. J Comput Chem. 2004 Jul 15;25(9):1157-74.

For nonstandard residues, arbitrary partial charges (such as obtained from the literature or parameter databases) can be specified. To do so:

1. run Dock Prep independent of Minimize Structure to perform any necessary tasks including charge addition (thus running Add Charge)
2. reassign the charge attribute of the atoms to the desired values (using Define Attribute, defattr, or setattr)
3. run Minimize Structure and turn off all options in the ensuing Dock Prep dialog, as the necessary tasks have already been performed

Lack of access to many settings. There is no way to specify several MMTK settings, including distance cutoffs. MMTK defaults are used. Evaluating all pairwise nonbonded interactions regardless of interatomic distance makes the calculation relatively slow.

Limited ability to use arbitrary parameters. It is difficult to change or add parameters. For nonstandard residues only, arbitrary partial charges can be specified. Experts can adjust parameters (other than charge) of standard residues and monatomic ions by editing files in bin/amber12/dat/leap/parm/ within the Chimera installation. The following parameter files are used:

• ff12SB: parm10.dat + frcmod.ff12SB + frcmod.ionsjc_tip3p
• ff03ua: parm99.dat + frcmod.ff03 + frcmod.ff03ua + frcmod.ionsjc_tip3p
• ff03.r1: parm99.dat + frcmod.ff03 + frcmod.ionsjc_tip3p

To add an element that is not already handled, it may also be necessary to create a file for that element in the MMTK atom database within the Chimera installation. For example, to handle Li⁺, there is a file lib/python*/site-packages/MMTK/Database/Atoms/li (where * is the appropriate python version number) containing the following:

name = 'lithium'
symbol = 'Li'
mass = 6.941