File

Alt-F

 

Menu File

[Open data file][Type of variables][Type of objects][Grid dimensions][Import Fields][Import Interactions][Import Activity][Quit]

 

This menu gives access to the basic operations involving file manipulation, as to open and import data files. In addition, the menu includes commands to define some properties of the data; as the type of variables, type of objects and the dimensions of the grid cage. Also the option to quit the program is in this menu.

 


File>>>Open data file

Alt-O

 

This command opens an Indigo Magic style file selection dialog, where the User can select the file to open. This file should be in GOLPE/SIMCA format, as described in appendix A.

 

File Selection Dialog

 

Files

This list shows all the files matching the filter pattern. Click on any of these files to select it. In addition, the list displays other accessible directories and allows the User to navigate through the directory tree. To see the contents of any descendent directory simply click on any item of the list. To see the contents of the parent subdirectory, click on the [..] item.

 

Select GOLPE file

Under this label the User can find three elements which can be used to select the file to open.

 

The Filter button brings up a dialog where the User can see and edit the filter pattern. This filter pattern string uses standard wildcards characters to define the files presented in the Files list. For example, in this case the filter pattern string is *.dat and therefore the list shows only files with the extension .dat (usually the GOLPE/SIMCA files have this extension). To show files with different extensions press the button and enter in this dialog the appropriate wildcards.

 

Once the selection is done press the OK button, and this file will be read. If the file has a improper format a error message will appear and the file will be refused. Press the Cancel button to abort the operation.

 

If the file is read for the first time, and the type of variables has never been defined the User will be prompted to define it.

 

Question

 

Press the Specify button to define the type of variables, otherwise, the file will be automatically refused.

 

See the File>>>Type of variables>>Modify command for details.


 

File>>>Type of variables

 

Type of Variables submenu

 


 

File>>>Type of variables>>List

 

Shows in the main window a summary of the type of variables in the active data file.


 

File>>>Type of variables>>Modify

 

This option displays a dialog window in which the User can choose the block to which the variables present in the data file belong.

 

Type of Variables dialog

 

#

A sequential index that identifies each block of variables. It is used extensively along the program.

 

Type

Depress the X Y N radio buttons to change type of this block of variables. Three types are possible:

GOLPE can handle a maximum of 10 different blocks of variables.

 

from

The sequential number of the first variable belonging to this block.

 

to

The sequential number of the last variable belonging to this block.

 

comment

In this field the User can enter some text to describe the block of variables.

 

Grid?

Select yes to indicate that this block contains grid variables (variables obtained from GRID, SYBYL or SPARTAN). The default is no.

 

In the example shown in the figure, the data file contains 3 blocks of variables:

  1. Steric field (probe 1). 3009 explanatory variables of grid type.
  2. Electrostatic field (probe 2). 3009 explanatory variables of grid type.
  3. Activity (Y). A single dependent variable.

 

When the OK button is pressed, the changes are applied to the file and stored in the disk. Changes can be applied at any time. After each change the data file is automatically reloaded and updated.


 

File >>>Variables type>>>Name

 

GOLPE allows the user to assign names to the variables, in data files containing up to 10.000 variables. This option is useful in order to identify the different variables in the PCA loadings, PLS loadings and PLS weights 2D and 3D plots.

 

{short description of image}

 

Variables

This is a list of all the variables names. The first time this option is selected, the variables are given the names VAR1, VAR2, VAR3...etc. In order to change those names, click on the name of the variable and it will be copied to the Variable name: input field.

 

Variable name:

This input filed remains empty until the User click on a variable name on the Variables list. Once one variable name is selected it can be edited, but the name will not be changed until the User press ENTER. In order to make easier the edition of many variable names, the input field works in overstrike mode and after pressing the ENTER key the following variable is selected.

 

Variable Names are stored in disk in a file named filename.dat.VarNames. As an alternative to the use of this command, the user can create or edit this file. The format is very simple: the first line contains the number of variables, which should match exactly the total number of variables in the dataset, and then exactly this number of lines, one for each variable, containing a label of no more than 20 characters each. The following example would be a valid file for a dataset with 5 X variables and 1 Y variable.

6

logP

MR

ES

B1

I1

Activity (pKi)

 

When the OK button is pressed, the variables names are stored in the disk and from this moment the names of the variables can be seen in the plots. Changes can be applied at any time.


 

File>>>Type of objects

 

Type of Objects menu

 


 

File>>>Type of objects>>>List

 

Shows in the main window a summary of the type of objects and the colors associated to them.


 

File>>>Type of objects>>>Modify (manual)

 

Often, the objects of a data set can be considered to belong to different types. For instance, they can be molecules of two chemical families, obtained from modifications of two different prototypes, or samples obtained from different sources, etc... In such cases it is interesting to highlight these peculiarities in the 2D and 3D objects plots, in order to identify any clustering of the objects related with those properties.

GOLPE allows the User to define different types of objects and to assign a different color to each type. Please notice that the types will be used only to give different colors to the objects in the plots and they have absolutely no influence in the results of the analysis.

In data files containing few objects the User can assign the colors directly. On the contrary, in data files with hundred or thousand of objects it would be more convenient to use the File>>>Type of objects>>>Modify (rule based) option.

 

Type of Object dialog

 

Object Type

The User can choose here the type (color) to assign. There are 10 options: white, red, green, blue, magenta, cyan, yellow, purple, brown and ivory.

 

Objects:

This is a list of all the objects present in the dataset. Each time the User click on an object name, the type of the object will change to the type currently active in Object Type. By default, before making any type change, all the objects are assigned to type 1 (white).

 

 

When the OK button is pressed, the object types are stored in the disk and from this moment they can be seen in the plots. Changes can be applied at any time.


 

File>>>Type of objects>>>Modify (rule based)

 

Often, the objects of a data set can be considered to belong to different types. For instance, they can be molecules of two chemical families, obtained from modifications of two different prototypes, or samples obtained from different sources, etc... In such cases it is interesting to highlight these peculiarities in the 2D and 3D objects plots, in order to identify any clustering of the objects related with those properties.

GOLPE allows the User to define different types of objects and to assign a different color to each type. Please notice that the types will be used only to give different colors to the objects in the plots and they have absolutely no influence in the results of the analysis.

In data files containing hundred or thousand of objects it is not practical to define the type picking one object at a time. When the type is associated with the name of the objects it is possible to define a rule, that can be then used to assign the type of the objects automatically.

 

Type of Object dialog

 

Rule definition

This input field contains initially a line of asterisks. The User should replace in this line the asterisks by the character # in those positions that distinguish the type of the objects. For example, if the data file contains a set of objects called X01, X02, X03... and other series called Y01, Y02, Y03.... the rule #************** will automatically assign different types to both series, since the first character is the key to identify the series to which belongs each object. The names of the objects can be more complicated, for instance they can be a first series of EA2748_A_01, EA2749_A_02, CAB347_A_03 ... and a second one of EA2748_B_01, EA2749_B_02, CAB347_B_03 ... In this case we can use the eighth character (A and B) to classify the objects in the two series, with the rule string *******#**********.

Formally, the rule works comparing the names of the objects only in those positions marked by the # character. If from the result of this comparison it is not similar to any previous object, it will be assigned to a new type. Since there is a maximum of 10 types (colors), type 11 will be assigned color 1 and so on.

Once the User has entered the string he should push the button Apply in order to carry out the type assignment. The results of the assignment can be inspected in the Objects names and types list. If the User is satisfied with the assignment he can press the OK button. Otherwise he can press the Cancel button and repeat the rule definition.

 

 

When the OK button is pressed, the object types are stored in the disk and from this moment they can be seen in the plots. Changes can be applied at any time.


 

File>>>Type of objects>>>Hide

 

In some data files there are dense clusters of objects that make difficult to see some particular object in the 2D and 3D plots. In such situations it is possible to toggle the hidden or visible status of some objects in the plots. It is important to notice that this status affects only the way the objects are shown in the plots. Hidden objects participate in any analysis in the same way that visible objects.

 

Type of Object dialog

 

In this dialog the visible status of the objects can be changed both picking individually the objects or using a rule definition.

 

Rule definition

This input field contains initially a line of asterisks. The User should replace in this line the asterisks by any character that identify the objects to hide. For example, if the data file contains the objects called X01, X02, X03, X04, Y01, Y02 and we want to hide the two last objects the rule Y************** will automatically assign these two objects a hide visibility status.

Formally, the rule works comparing the names of the objects only in those positions not containing an asterisk. If from the result of this comparison an object is found similar to the rule, it is assigned an hidden status, if not it is assigned a visible status.

Once the User has entered the string he should push the button Apply in order to carry out the visibility status assignment. The results of the assignment can be inspected in the Objects names list. If the User is satisfied with the assignment he can press the OK button. Otherwise he can press the Cancel button and repeat the rule definition.

 

In addition the user can click on the names of individual objects in the Objects names list. Each click will switch the visible-hidden status of this object.

 

 

When the OK button is pressed, the object visibility status are stored in the disk and from this moment they can be seen in the plots. Changes can be applied at any time.


 

File>>>Type of objects>>>Define spectrum

 

In GOLPE it is possible to color the objects according to a chromatic scale that represents the values of a certain variable. For example, it is possible to color the objects according to the activity in a PCA scores plot, thus showing the LV to which this property is related, etc... In 3D objects plots, this color scale adds a fourth dimension, allowing to represent an additional variable, impossible to visualize by any other method.

 

In order to define the spectrum, the first step is to choose the variable that will be used to color the objects. This can be any active variable in the data set. This variable can belong to any X or Y block but not to a N block. In addition, it should exhibit a minimum variation (it can not take constant values in the series). By default, the first Y variable in the dataset is choosen.

 

Define Spectrum Dialog I

 

After pressing the OK button the following dialog appears:

 

Define Spectrum Dialog II

 

Minimum value

Maximum value

The User can move these slides to define the maximum and the minimum between of which the spectrum will show color variation. Objects with values higher than the maximum and lower than the minimum will be assigned the to and from colors. Objects with values into the range defined by these two values can be draw in the plots with colors that take intermediate values between the color defined as from and the color defined as to.

 

from

to

In these menus, the User can choose the colors associated with low values of the spectrum variable (from) and with high values of the spectrum variable (to). Both color should be different. The choices are red, blue and green.

 

 

When the OK button is pressed, the spectrum is saved to disk. From this moment, in the 2D and 3D plots of objects there is the option to color the points according to the defined spectrum.


 

File>>>Grid dimension

 

Grid dimension submenu

 


 

File>>>Grid dimension>>List

 

This command writes in the main window the x, y, z coordinates of the grid cage and the number of grid points for each axis.


 

File>>>Grid dimension>>>Specify

 

Opens a dialog window in which the User can define the dimensions of the grid cage.

 

Grid dimension dialog

 

points

The number of grid points defined in the cage for this axis. The total number of grid points can be calculated as the product of the points for the X, Y and Z axis and should correspond to the total number of variables included in grid blocks. In the example, the blocks defined as grid variables should contain 17x11x7=1309 variables each.

 

minimum

The lower boundary of the cage in this axis, in Angstroms.

 

maximum

The upper boundary of the cage in this axis, in Angstroms.

 

 

When the button OK is pressed this grid cage definition is applied to all the blocks of variables which were defined as grid variables, and stored in disk. The size of the cage should be defined before displaying any grid plot or performing grouping of variables.


 

File>>> Import Fields

 

Import Fields submenu

 

GOLPE does not include any method to generate field data on its own. The GOLPE/SIMCA files, which are the standard input files in GOLPE, are obtained by importing data from other programs.

 

The current release of GOLPE can import Molecular Interaction Fields from SYBYL, GRID and SPARTAN. The importation produces standard GOLPE/SIMCA files which can then be read with the File>>>Open data file command. Please consult the appendices to learn more about how generate suitable files for importing into GOLPE.


 

File>>> Import Fields>>>Sybyl (.qab file)

 

IMPORTANT: Before using this command, the .qab files should have been already generated in SYBYL, following the steps described in theappendices.

 

This command opens a dialog like this:

 

SYBYL import dialog

 

Find...

Press this button to open a standard file selection dialog. The file selected will be then presented in the input line inmediatly to the left to the button pressed. See the File>>>Open data file command for details about the file selection dialog.

 

QAB input file (.qab)

Nameof the SYBYL qab file to import. Refer to the appendices to learn how to generate this file.

 

GOLPE new file (.dat)

Name of the new file in GOLPE/SIMCA format that will be generated after the importation. Our advice is to enter a name long enough to be informative, and to include the extension .dat. GOLPE will accept any name, even if it overwrites another file or it does not include the extension .dat.

 

Spreadsheet ASCII file (.txt)

Name of an ASCII text file which contains the names of the objects (molecules). This file can be created in SYBYL, from the Molecular Spreadsheet (MSS), using the command File>>>Write Report, and then typing the name of the export file.

The spreadsheet file is optional. To instruct GOLPE to look for this file and to make sensitive the input field, click the check button use.

 

Region file (.rgn)

Name of a region file in SYBYL format that contains the size of the cage in which the CoMFA analysis was performed. This file, characterized by the .rgn extension, is automatically generated by SYBYL during the CoMFA analysis.

 

The region file is optional but, if no such file is found the size of the cage should be defined later using the File>>>Grid dimension>>>Specify command. To instruct GOLPE to look for this file and to make sensitive the input field, click the check button use.

 

 

When the button OK is pressed, a new file with GOLPE/SIMCA format, containing all the grid variables generated in SYBYL will be produced. Remember that before using this data file in GOLPE it should be loaded using the File>>>Open data file command.


 

File>>> Import Fields>>>GRID-kont

 

GOLPE allows users to work directly with GRID kont files, without post processing the file. Binary GRID kont field file may be imported together with the kout structure of the target. In this context, GOLPE may be used as a 3D graphical interface to the GRID program.

 

IMPORTANT: Before to use this option GRID kont output files should have been generated. Refer to appendix C for further information about how to import data from GRID.

 

This command opens a dialog like this:

 

GRID import dialog

 

Find...

Press this button to open a standard file selection dialog. The file selected will be then presented in the input line inmediatly to the left to the button pressed. See the File>>>Open data file command for details about the file selection dialog.

 

GRID kont file (.kont)

Name of the GRID .kont file to import. Refer to the appendices to learn how to generate this file.

 

GOLPE new file (.dat)

Name of the new file in GOLPE/SIMCA format that will be generated after the importation. Our advice is to enter a name long enough to be informative, and to include the extension .dat. GOLPE will accept any name, even if it overwrites another file or it does not include the extension .dat.

 

When the OK button is pressed, GOLPE reads the selected file and writes a the newly generated file in GOLPE/SIMCA format.

 

 

In GRID it is possible to work with a single target (molecule) and several probes or with several targets (molecules) and one probe. If we have T targets, P probes and G grid variables, it is possible to generate two kinds of matrices:

 

Target matrix All the information associated with a target (the variables obtained with different probes) is included in the same vector. The resulting matrix contains T objects and PxG variables.
Probe matrix The information associated with each target-probe interaction is included in a different vector. The resulting matrix contains TxP objects and G variables.

 

GOLPE will automatically detect when a target has been explored by more than one probe, and presents a dialog window asking the User for the desired kind of matrix to obtain.

 

Import GRID files dialog

 

Press the Yes button to obtain a probe matrix or the No button to obtain a target matrix. Of course the choice depends on the problem under study.

 

Notice that, to use the imported file in GOLPE it is necessary to load it with the File>>>Open data file command.


 

File>>> Import Fields>>>SPARTAN

 

GOLPE allows the User to import a set of SPARTAN ASCII files defining Molecular Electrostatic Potential fields or other field properties. Please refer to the appendices to learn how to generate the starting files in SPARTAN.

This command opens a dialog like this:

 

SPARTAN import dialog

 

Find...

Press this button to open a standard file selection dialog. The file selected will be then presented in the input line inmediatly to the left to the button pressed. See the File>>>Open data file command for details about the file selection dialog.

 

SPARTAN grid file/s (.file)

Name of the SPARTAN file or files to import. The User can enter simply one filename or a pattern representing a set of filenames, one for each compound in a series. For example, if the User want to import the files:

we can write in the input line:

f0###.file

GOLPE will try to import files that match these pattern and include in the same GOLPE file consecutively, each one as a different object. The name of the objects in the file will correspond to the characters mapped by the ### characters. In the example, the objects will be given the names 01a, 01b, 02a ... 45z

Refer to the appendices to learn how to generate a set of files in SPARTAN.

 

GOLPE new file (.dat)

Name of the new file in GOLPE/SIMCA format that will be generated after the importation. Our advice is to enter a name long enough to be informative, and to include the extension .dat. GOLPE will accept any name, even if it overwrites another file or it does not include the extension .dat.

 

When the OK button is pressed, GOLPE reads the selected file or files and writes a newly generated file in GOLPE/SIMCA format.


 

File>>> Import Interactions

 

Import Interactions submenu

 

GOLPE does not include any method to generate field data on its own. The GOLPE/SIMCA files, which are the standard input files in GOLPE, are obtained by importing data from other programs.

 

The current release of GOLPE can import ligand-receptor analysis of interaction obtained with the ANAL module of AMBER. and with MSI's DISCOVER. The importation produces standard GOLPE/SIMCA files which can then be read with the File>>>Open data file command. Please consult the appendices to learn more about how to generate suitable files for importing into GOLPE.

 


 

File>>> Import Interactions>>>AMBER

 

The current release of GOLPE can import ligand-receptor analysis of interaction obtained with the ANAL module of AMBER. The values of the ligand-receptor interaction, usually partitioned as electrostatic and van der Waals, per-residues contribution, can be used in the context of a COMBINE analysis. See C.Perez, M.Pastor, A.R.Ortiz, F.Gago, J.Med.Chem. 41, 836, (1998) and references therein for further reference.

The command opens a dialog like this:

 

AMBER import dialog

 

Find...

Press this button to open a standard file selection dialog. The file selected will be then presented in the input line immediately to the left to the button pressed. See the File>>>Open data file command for details about the file selection dialog.

 

AMBER ANAL file/s (.outa)

Name of the ANAL output file or files to import. The User can enter simply one file name or a pattern representing a set of file names, one for each compound in a series. For example, if the User want to import the files:

we can write in the input line:

f0###.outa

GOLPE will try to import files that match these pattern and will include them in the same GOLPE file consecutively, each one as a different object. The name of the objects in the file will correspond to the characters mapped by the ### characters. In the example, the objects will be given the names 01a, 01b, 02a ... 45z

Since outa files are very large, the files can be compressed with gzip. GOLPE can handle a set of compressed files, decompressing the file only when required to save disk space.

Refer to the appendices to see an example of an ANAL command file used to obtain appropriate output files.

 

GOLPE new file (.dat)

Name of the new file in GOLPE/SIMCA format that will be generated after the importation. Our advice is to enter a name long enough to be informative, and to include the extension .dat. GOLPE will accept any name, even if it overwrites another file or it does not include the extension .dat.

 

Number of the Ligand (i.e. 999):

The outa file contains all the interactions between every couple of residues (group of atoms, in AMBER terminology) in the protein. In COMBINE analysis, the only interesting interactions are those between the ligand and all the rest of residues.

In this line the User should enter the residue number that identifies the ligand in the outa file. If you are importing a set of files, make sure that the number that identifies the ligand is the same in all of them.

 

Interactions to import:

Select one or more types of interactions. Each type will generate a contiguous block of variables. The import produces also a variable type definition file and therefore the different blocks or variables will be recognized automatically when the newly generated file was imported into GOLPE.

Some force fields used in AMBER lack some of these types of interactions, for example, if AMBER is used with the parm94 force field definition, no hydrogen bond interaction energy will be computed. Refer to AMBER documentation for further reference.

 

When the OK button is pressed, GOLPE reads the selected file or files and writes a newly generated file in GOLPE/SIMCA format.

 


 

File>>> Import Interactions>>>DISCOVER

 

The current release of GOLPE can import ligand-receptor analysis of interaction obtained with MSI DISCOVER. The values of the ligand-receptor interaction, usually partitioned as electrostatic and van der Waals, per-residues contribution, can be used in the context of a COMBINE analysis. See C.Perez, M.Pastor, A.R.Ortiz, F.Gago, J.Med.Chem. 41, 836, (1998) and references therein for further reference.

The command opens a dialog like this:

 

DISCOVER import dialog

 

Find...

Press this button to open a standard file selection dialog. The file selected will be then presented in the input line immediately to the left to the button pressed. See the File>>>Open data file command for details about the file selection dialog.

 

DISCOVER file/s (.out)

Name of the DISCOVER output file or files to import. The User can enter simply one file name or a pattern representing a set of file names, one for each compound in a series. For example, if the User want to import the files:

we can write in the input line:

f0###.out

GOLPE will try to import files that match these pattern and will include them in the same GOLPE file consecutively, each one as a different object. The name of the objects in the file will correspond to the characters mapped by the ### characters. In the example, the objects will be given the names 01a, 01b, 02a ... 45z

Refer to the appendices to see an example of an DISCOVER DSL command file used to obtain appropriate output files.

 

homology key(.txt)

Often, the out files imported correspond to the same receptor. However, in some situations the out files can correspond to closely related proteins. In this case GOLPE will assume by default that residues with the same numeric code are equivalent. This is not true in all cases and the User can define a more sophisticated way to define residues equivalences by introducing a "homology.key" file. This field is optional and if the User left it void the above default method will be used.

The homology key is a ASCII text file that defines the residues equivalences (homology) between different proteins. It is intended to be obtained adapting the output of standard sequence homology programs. The format is very simple: the file may contain at least as many sections as proteins types (with different sequences) are being imported. Each section contains a unique number starting with "1" and a residue sequence which can be split along many lines in the file. The file may contains any number of spaces. The file can contain comment lines starting with characters "!" or "#" or void lines. Spaces and asterisks are ignored.

This is an example of a valid homology key:

# example of homology key used by GOLPE to decide how to align proteins

# in a PCA/COMBINE example

1

EADCGLRPLFEKKSLEDKTERELLESY-IVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLY

PPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPD

RETAASLLQAGYKGRVTGWGNLKET-GQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEG

DSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE-------------------

-------------------------------------

2

----------------------------IVGGQECKDGECPWQALL-INEENEGFCGGTILSEFYILTAAHC---

-------LYQAKRFKVRVGDRNTAAEEGGEAVHEVEVVIKHNRFTKETYDFDIAVLRLKTPITFRMNVAPACLPE

RDWAESTLMTQKTGIVSGFGRTHEKGRQSTRLKMLEVPYVDRNSCKLSSSFIITQNMFCAGY---DTKQEDACQG

DSGGPHV--TRFKDTYFVTGIVSWGEGCARKGKYGIYTKVTAFLKWIDRSMKTR-TRKLCSLDNGDCDQFCHEEQ

ASVVCSCARGYTLADNGKACIPTGPYPCGKQTLER-X

3

----------------------------IVGGYTCGANTVPYQVSL---NSGYHFCGGSLINSQWVVSAAHC---

---------YKSGIQVRLGEDNINVVEGNEQFISASKSIVHPSYNSNTLNNDIMLIKLKSAASLNSRVASISLP-

---TSCASAGTQCLISGWGNTKSSGTSYPDVLKCLKAPILSDSSCKSAYPGQITSNMFCAGY---LEGGKDSCQG

DSGGPVV------CSGKLQGIVSWGSGCAQKNKPGVYTKVCNYVSWIKQTIASN-X-------------------

-------------------------------------


The order of the sections and the molecule code are irrelevant. When GOLPE imports a out file, it read the sequence section and tries to find a matching line in the homology key. If no line in the homology key matches the sequence for this protein an error message will be shown.

Some homology programs, like CLUSTAL, output the homology results as separate blocks of sequences. To help the User on converting these output, this format is also accepted:

1

EADCGLRPLFEKKSLEDKTERELLESYIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLI

2

---------------------------IVGGQECKDGECPWQALLINEE-NEGFCGGTIL

3

---------------------------IVGGYTCGANTVPYQVSLNSGY---HFCGGSLI

1

SDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWR

2

SEFYILTAAHCLYQAK--------RFKVRVGDRN-TAAEEGGEAVHEVEVVIKHNRF-TK

3

NSQWVVSAAHCYKS----------GIQVRLGEDN-INVVEGNEQFISASKSIVHPSY-NS

1

ENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETG--QPS

2

ETYDFDIAVLRLKTPITFRMNVAPACLPERDWAESTLMTQKTGIVSGFGRTHEKGR-QST

3

NTLNNDIMLIKLKSAASLNSRVASISLP-----TSCASAGTQCLISGWGNTKSSGTSYPD

1

VLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNR

2

RLKMLEVPYVDRNSCKLSSSFIITQNMFCAGYDT---KQEDACQGDSGGPHVTR--FKDT

3

VLKCLKAPILSDSSCKSAYPGQITSNMFCAGYLE---GGKDSCQGDSGGPVVCS------

1

WYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE-------------------

2

YFVTGIVSWGEGCARKGKYGIYTKVTAFLKWIDRSMKTRTRKLCSLDNGDCDQFCHEEQA

3

GKLQGIVSWGSGCAQKNKPGVYTKVCNYVSWIKQTIASN---------------------

1

----------------------------------

2

SVVCSCARGYTLADNGKACIPTGPYPCGKQTLER

3

----------------------------------

The results of the homology analysis will be written to a file called filename.dat.HomologyLog, where the name assigned by GOLPE to the variables representing different ligand-residue interactions is specified in detail.

GOLPE will produce a variable for each different residue in the set of files. If a homology key file is present, it will add a variable for every character in the sequence definition that is different from "-" in, at least, one of the proteins. If a certain proteins lacks one residue, GOLPE will put a value of 0.00 in this variable and not a missing value, since the absence of the residue is actually informative.

 

GOLPE new file (.dat)

Name of the new file in GOLPE/SIMCA format that will be generated after the importation. Our advice is to enter a name long enough to be informative, and to include the extension .dat. GOLPE will accept any name, even if it overwrites another file or it does not include the extension .dat.

 

Name of the Ligand (i.e. LIG):

The out file contains the interactions between many couples of residues in the protein. In COMBINE analysis, the only interesting interactions are those between the ligand and all the rest of residues.

In this line the User should enter the residue name that identifies the ligand in the out file. If you are importing a set of files, make sure that the residue name that identifies the ligand is the same in all of them.

 

Interactions to import:

Select one or more types of interactions. Each type will generate a contiguous block of variables. The import produces also a variable type definition file and therefore the different blocks or variables will be recognized automatically when the newly generated file was imported into GOLPE.

 

When the OK button is pressed, GOLPE reads the selected file or files and writes a newly generated file in GOLPE/SIMCA format.


 

File>>> Import Activity

 

Quite often, the values of the dependent variables are added a posteriori to the data. Moreover, these values are often a measure of the biological activity of the compounds and the crude values require to be transformed to logarithmic scale. This command allows to import such data and performs the required transformations in a simple and straightforward way.

The command opens a dialog like this:

 

Activity import

 

Find...

Press this button to open a standard file selection dialog. The file selected will be then presented in the input line immediately to the left to the button pressed. See the File>>>Open data file command for details about the file selection dialog.

 

Activity File (ASCII)

Enter here the name of an ASCII file containing one line for each compound and one or two columns: separated by spaces or tabs:

The following examples is a valid ASCII activity file:

With a first column of labels

mol1 0.34

mol2 0.56

mol3 0.01

mol4 0.97

Without a first column of labels

0.34

0.56

0.01

0.97

Please notice that the first column is only a reminder for the User. GOLPE will not compare these names with the actual names of the objects in the file. The first value in this file will be assigned to the first object (in the order listed in the first read of the file), the second to the second object and so on...

 

pK (-log)

If this control is selected, the numerical data x will be converted to -log(x). An error will be shown if any of the values is zero or negative. The biological data is usually provided in milimolar, micromolar or nanomolar concentrations. In this dialog is possible to select the appropriate units for the data.

 

Skip first field

As mentioned above, the first column can be used to write a label which reminds the User the name of the objects. If the file contains such a column, select this control to prevent GOLPE to read it as if it was numerical data.


 

File>>>Quit

Alt-Q

Select this option to exit from GOLPE. A dialog window will appear to confirm the exit.

 

Exit dialog

 

Press OK button to exit from GOLPE or the Cancel button to close the dialog window and continue working.