General description of the COMO program.

COMO is a new program for molecular replacement calculations, using the combined molecular replacement protocol (L. Tong (1996) Acta Cryst. A52, 782-784). It supports almost all the functionalities of my earlier TF program, which is part of the Replace package (L. Tong (1993) J. Appl. Cryst. 26, 748-751). In addition, COMO supports the calculation of cross rotation functions (by the Crowther fast rotation function) (R.A. Crowther (1972) The Molecular Replace Method, M.G. Rossmann Ed.) that was available as part of the GLRF program (L. Tong and M.G. Rossmann (1990) Acta Cryst. A46, 783-792). In summary, COMO is a complete program for the structure determination by the MR method, starting from a search atomic model. In this regard, COMO can replace the use of the TF program for most calculations.

However, COMO currently does not support the calculations of self rotation functions, locked (self and cross) rotation functions, locked translation functions (L. Tong (1996) Acta Cryst. A52, 476-479), or the contouring of the RF maps. These calculations are done very nicely in the GLRF program.

Combined molecular replacement is a protocol to carry
out a limited six-dimensional search, covering both the rotational and translational
degrees of freedom, for the solution to a MR problem
(L. Tong (1996) Acta Cryst. A52, 782-784). The
basic idea behind this is that the correct orientation for the search model
will give a relatively high value in the rotation function. However, this
orientation may not correspond to one of the *peaks* in the rotation
function. Experiences suggest that this is oftentimes the case, where the
correct orientation gives a high RF value, but is 5—10° away
from the nearest peak in the RF. A traditional TF calculation using only
the *peaks* in the RF will likely not succeed in finding the MR solution.

Some of the features that are supported by the COMO program include–

- Use of large terms for the calculation of the translation function. In several cases, this usage has helped to reveal the correct solution, whereas a TF calculation using all reflections gave only solutions that have serious packing problems.
- Automatic packing check to eliminate those MR solutions that have seriously overlap among the molecules. We believe this is a very important feature of the COMO program (This was also supported in the TF program). This helps eliminate those MR solutions that can not be correct.
- The program supports the automatic sampling of a family of structures for MR. This family could be a collection of structures from homology modeling, or a collection of crystal structures with various degrees of homology to the unknown structure, or a collection of structures with various conformational across a flexible linker (such as the elbow angle in Fab, or small lobe movement in protein kinases).
- The program can automatically search for several copies of a given model in the crystal cell, one after another.
- The program can read in the rotation function map generated by the GLRF program.

Like the Replace package, the input to the COMO program are free-formatted and keyword-based. However, there are also significant differences to the input structure of the COMO program. The inputs are grouped into blocks, and currently the following blocks are supported –

- Crystal (for the input of crystal information)
- Model (for model information)
- RF (for rotation function information)
- TF (for translation function information)
- SF (for structure factor calculation information)
- Solution (for output of MR solutions)

The program will perform the relevant calculations at the end of each input block (with the exception of the Model and RF blocks, see below). Consequently, the blocks can be repeated in the input file. For example, one could have the following sequence of blocks for input – Model, TF, Model, RF, TF, Solution. The first Model-TF combination defines a molecule with known orientation and searches for its position by TF. The second Model-RF-TF defines a molecule with no known information and carries out both RF and TF calculations. Finally, the MR solutions from both calculations are output with the Solution block.

For the Model block, the calculations are performed
*immediately* after each command, rather than at the end of the entire
block. For the RF block, the calculation will generally not be done at the
end of the input to this block (but also see the GO command in the RF block).
The actual RF calculation will be initiated during the MR calculation as
necessary.

The program will produce two kinds of error messages. A Warning error message is given to potential problems with either the user input or other parameters in the calculation. The calculation will continue, but the user should examine the Warning message with some care. A Fatal error message will stop the program execution.

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© copyright 2000-2003 by Liang Tong.