Optional Parameters

Input parameters

-userFrags

This option is similar to the -in flag except that it is for passing pregenerated fragments rather than for passing whole molecules. Using this flag skips the initial cutting apart stage; fragments are passed directly into the conformer generation and database construction phase. Fragments passed using this flag will be added to the database in the order in which they are read (no resorting occurs). It is important to note that the -in and -userFrags flags can be used together.

-userUnique

This flag allows you to specify a database you would like to use for duplicate removal. The fragments in the specified database will be determined as unique; if the fragment is seen again in the current run, those fragments will be skipped rather than incorporated into the new database.

Output parameters

-prefix

This string flag determines the prefix of the info, log, report, param, and output files. For example, if -prefix is set to foo, then the output files will include foo.info, foo.log, foo.report, and foo.param. [default = chomp]

-dots

When this flag is set, the program will write a series of dots (.) to the terminal (stdout/cout) to track the progress of the program. The dots are written in two phases: first as the molecules are cut apart and organized and second as the conformers are generated and the database is written. [default = true]

Control parameters

-smarts

This flag specifies the SMARTS file for user-defined fragmentation methods. This flag is optional, as Chomp contains a default fragmentation algorithm. The SMARTS strings should identify two atoms that are joined by a bond that the user wants to be broken during fragmentation. Each SMARTS string should be placed on its own line in the -smarts file. SMARTS specified with this flag replace rather than augment the default fragmentation rules.

-capAttach

When a fragment is generated with multiple attachment points, this flag controls whether all the related fragments can be generated by capping one or more of the attachment points with a hydrogen. This can generate many more fragments, but is quite efficient. [default = true]

-flipper

This flag controls whether the flipper algorithm is used to generate the 2^N specific isomers by enumerating the stereo on unspecified stereocenters. The flipper flag takes an integer indicating the N in the 2^N isomers that can be generated from N stereocenters. If the stereocenters in the molecule exceed N, then 2^N random unique isomers are sampled from the available isomers. By default, no more than 32 isomers will be generated from any molecule. [default = 5]

-forceFlip

The -forceFlip flag causes all stereocenters in a ligand to be enumerated, even if they had specified stereo on the input structure. While this can generate fragments that are not specifically represented in the input molecules, it is also a means of exploring more of the chemical fragment space. [default = false]

-flipN

This flag controls whether or not nitrogen atoms with potential stereochemistry are enumerated. Some nitrogens atoms have real stereochemistry, while most others are easily invertible in solution. In fragment replacement, specific invertible static nitrogen structures are often being compared to carbon-based structures that are not invertible. It can therefore be useful to enumerate the nitrogen structures in the database even though they are interconvertible in solution. For this reason, the flag here controls whether or not nitrogen atoms with potential stereochemistry are enumerated. [default = true]

-omega

This flag controls whether the conformer generation using the OMEGA conformers is applied to the fragments. This flag has two important repercussions. First, by turning it off, the process can be stopped after the relatively quick fragmentation phase. This allows users to examine the fragments that are automatically written to an intermediate SMILES file before paying the high cost of generating conformers. Second, you can choose to replace the OMEGA algorithm with sampling conformers from known structures using the -readConfs flag.

-readConfs

This flag allows users to specify a 3D structure file from which the database generation algorithm will sample conformers. For each fragment generated in the cutting algorithm, all examples of the fragment’s conformers that are present in the molecule file specified by this flag will be added as conformers and saved in the BROOD database. Identical conformers are recognized and duplicates are removed. If you have access to a large database of small-molecule crystal structures, this flag can be used to sample conformers from that database rather than using the OMEGA algorithm.

Note

The input molecules used to generate the fragments (from the -in or -userFrags flags) do not need to be the same as the input molecules specified with this flag.

-primaryFrag

This flag indicates that Chomp should only process the smallest possible fragments with the given fragmentation pattern. It is primarily for fragmentation applications unrelated to BROOD.

Fragment selection parameters

-filter

This is a complex flag that specifies both whether the default filter should be applied to the fragments with the values (True and False). The -filter flag can also be used to specify a filter file describing a non-default filter to be used to filter the fragments. For additional information on filtering, please see the documentation for the filter product.

-minFrequency

During the breaking of input molecules into fragments, the number of source molecules from which a fragment can be extracted is tracked. This flag indicates the minimum number of source molecules that are required in order for the fragment to be retained. The frequency in this case is normalized as a percentile where 99 indicates the most common fragments and 0 indicates the least common fragments. By default, all fragments are retained. [default = 0]

-maxDegree
-minDegree

While the fragments in the default BROOD database contain between one and three attachment points, this is a heuristic choice based on search efficiency and not a requirement. The -minDegree and -maxDegree flags specify the range of acceptable attachment points for fragments generated by Chomp. [default = 1,3]

-maxMolWt

This is a simple flag that allows the user to specify the maximum molecular weight of any fragment generated by Chomp. [default = 350.0]

-maxHvy
-minHvy

These flags specify the range of heavy atoms allowed in fragments generated by the CHOMP algorithm. [default = 0,15]

-maxChiral

This flag allows you to specify the maximum number of chiral centers (both atom and bond centers) in a fragment. While there are many drugs and other useful molecules with a large number of stereocenters, they are often added for a specific purpose and should not be suggested lightly in a design setting. For this reason, fragments with many chiral centers may be undesirable in some databases. This flag allows the user to efficiently eliminate these fragments. [default = 3]