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# Calculation Methods Molecular mechanics calculations commonly include several steps: Model construction Model association with a force field The proper calculations Analysis of the results The main function of the graphical shell is to assist model construction and association with a force field. The calculations and analysis can be performed either in the graphical interface or using external programs. ### Force Field association The association of molecular mechanics types is a process that cannot be completely automated. Although we tried to make it as simple as possible, it should be always controlled by the user. The model association with a force field is based on the assignment of each atom to a molecular mechanics type. The atomic type defines the force field parameters to be used in calculations of forces exerted on it. Since different force fields are described by different force parameters and different molecular mechanics types, a mechanism is required to associate atoms with types and partial charges for each supported force field. The problem of correct association is complex since there are many molecular mechanics types. Our approach to the problem relies on the following. Molecular models are built from fragments (molecules and residues) present in our database. In these fragments, all atoms are described by Fine types. A Fine type is the most general (the most detailed) molecular mechanics type of atoms. Basically, each atom in each fragment can have an unique Fine type. There are tables that specify molecular mechanics types and partial charges for a given Fine type and force field. These tables are included in the mlm format. Let us consider the following record as an example.
@Table | MM_types
str | str | double | str | double
Fine_type | AMBER94 |  | OPLS |
CH3_propane | CT | - | 10 | 0
H3C- | HC | - | 0 | -
-CH2- | CT | - | 9 | 0
H2C- | HC | - | 0 | -
Here, four carbohydrate types were described. They were associated with two types of the AMBER94 force field and two types of the OPLS force field. Note that four types are reduced to two ones in radically different ways. The AMBER94 does not distinguish terminal and bridging atoms in carbohydrate chain. Carbon and hydrogen atoms correspond to the CT and HC types. At the same time, the OPLS distinguishes terminal and bridging atoms. Terminal methyl groups correspond to type 10, while methylene groups correspond to type 9. The OPLS has no aliphatic hydrogen atoms, which corresponds to the united-atom model. Missing types are assigned to type 0. Undefined parameters are marked by dash. In the above example, the charges on missing types in the OPLS and all charges in AMBER94 are undefined. If charges are undefined in the table, the values specified in the fields of atoms are used. If they are undefined there too, zero values are used. Using such tables, the program can associate atoms with types appropriate for a force field. An initial association is made during the model construction, since the fragments, from which the model is constructed, can be associated with a force field. This should be taken into account so as not to build a discordant model from elements with different force fields. The user can force the model to use the same force field (Edit > Assign FF type menu). This can also lead to complications. Note that force fields are defined only for some classes of substances and forcing a particular force field has no effect for the molecules where this force field is unavailable. Finally, even if all types are defined, the proper force field can be missing in the current version of the program. Unfortunately, force field association is a weak point in molecular mechanics modeling. Development of a unique force field for the studied molecules can be the very desirably. Currently, the program supports the molecular mechanics fields AMBER94 and OPLS as well as fields for certain solvents (e.g., H2O, MeCN, DMSO, and CCl4). Water is considered as a particular substance. The water force field can be retrieved from the \bin\moldb\H2O.mmol file. By default, this file describes the flexible SPC water model. The force field data are stored in the \MolMeccano\ForceField folder. The file default.ff defines active force fields. The file with the name of the current force field and ff extension includes the names of files with the force field parameters. In addition, it specifies dielectric permittivity, 1–4 scaling factors for electrostatic and for van der Waals interactions, and the combinatorial rule used to calculate parameters of van der Waals interactions between heterogeneous atoms (arithmetic or geometric). Whenever a molecular mechanics simulation is started, these files are read. Accordingly, the user can change a force field type or its specific parameters without restarting the program. Let us exemplify an association of molecular mechanics types. Open the Sequence editor ; press the –CHMe– button. An isobutane molecule appears. Store it in the i Butane.hin file; press the –CH2– button. An isopentane molecule appears. Store it in the i Pentane.hin file; checking the types of atoms in these files shows that they are CT and HC in one case or numeric values in the other case. By default, the –CHMe– residue is associated with the AMBER94 field; while adding the –CH2– residue changes the association to the OPLS-AA field. This example shows that care should be taken during model construction and the field in effect should be checked after each step; change the association back to AMBER94 by selecting it in the Edit > Assign FF type menu. If the model is saved, we can check that the atoms were assigned to the CT and HC types; change the force field again by selecting OPLS in the Edit > Assign FF type menu. Note that all atoms are described by numeric values now. Moreover, carbon atoms are assigned to different types! The OPLS distinguishes methyl groups depending to what they are attached to. That is why the –CHMe– and –CH2– groups have methyl stubs. These methyl groups belong to different Fine types, which allows their correct conversion to OPLS types; hydrogen atoms are assigned to type 0 in our model. This means that such atoms are missing in the OPLS field. Hence, they can be removed from the model. Note that the removal of hydrogen atoms is irreversible. It is recommended to save the model before this operation. Selecting the Edit > Strip menu item removes hydrogen atoms. ### Model checking Several tricks can be useful to control the validity of the constructed model. First, pay attention to the information panel (Analyze > Information > Model or the button). Check if the boundary conditions have been specified and the parameters are valid. Check the associated force field. Check if chemical bonds are specified. Typically, the absence of bonds results from reading a model from a file that lacks them. Usually, the program tries to assign bonds automatically but does not always succeed. Check the number of different molecular types involved in the model. Do their molecular formulas and molecular weights look sensible? Are the charges on the molecules integer? Fractional charges commonly indicate incorrect force field association. Examine the model in mmol format. This format describes both the model and the force field associated with each atom and bond. Of course, it is not easy to check the force field in a large model. It is recommended at least to pay attention to zero force field parameters, which are commonly marked by comments with exclamation points. The torsion angles often have zero values, while the constants of valence angles and bonds can hardly be zero. After the calculation is started, a warning about missing force field parameters can appear. Usually, such warning appears once for the first missing parameter. The full list of missing parameters can be viewed in the log file (_log.txt) or in the Log section of the information panel.
| Copyright 1996, 1999, 2005, 2007 by: Alexander Lyubartsev, Aatto Laaksonen, Alexey Nikitin. Department of Physical Chemistry, Stockholm University. All rights reserved. Copyright 2006, 2007 Agile Molecule. All rights reserved.