Structure entry system

The structure entry system was designed to accommodate rapid error-free structure entry, with much consideration given to structure diagram cosmetics. It was also designed so that it could be easily incorporated into the compound registry and search system with little or no modification. For that reason, we will present an operational overview of the graphical structure entry system, focusing in particular on its use in the creation of the structural database. 

In 1986, David Weininger created the SMILES Simplified Molecular Input Line Entry System) notation at the US Environmental Research Laboratory, USEPA, Duluth, MN, for chemical data processing. The chemical structure information is highly compressed and simplified in this notation. The flexible, easy to learn language describes chemical structures as a line notation [20, 21]. The SMILES language has found widespread distribution as a universal chemical nomenclature... 

The JME Editor is a Java program which allows one to draw, edit, and display molecules and reactions directly within a web page and may also be used as an application in a stand-alone mode. The editor was originally developed for use in an in-house web-based chemoinformatics system but because of many requests it was released to the public. The JME currently is probably the most popular molecule entry system written in Java. Internet sites that use the JME applet include several structure databases, property prediction services, various chemoinformatics tools (such as for generation of 3D structures or molecular orbital visualization), and interactive sites focused on chemistry education [209]. 

Chemical identity may appear to present a trivial problem, but most chemicals have several names, and subtle differences between isomers (e.g., cis and trans) may be ignored. The most commonly accepted identifiers are the IUPAC name and the Chemical Abstracts System (CAS) number. More recently, methods have been sought of expressing the structure in line notation form so that computer entry of a series of symbols can be used to define a three-dimensional structure. For environmental purposes the SMILES (Simplified Molecular Identification and Line Entry System, Anderson et al. 1987) is favored, but the Wismesser Line Notation is also quite widely used. 

Toropov AA, Toropova AP, Mukhamedzhanova D, Gutman I (2005a) Simplified molecular input line entry system (SMILES) as an alternative for constructing quantitative structure-property relationships (QSPR). Indian J. Chem. Sect A. 44 1545-1552. 

The most advanced computer version, CLOGP-3, is really a log P modelling system that is, all the numerical data to operate it resides in tables which can conveniently be changed or updated. Figure 2 illustrates two kinds of structure entry which can provide the suitable connection table input for benzoic acid ... 

Entry System Structure" No. of studied complexes Figand No. and type of donor atom(s) X value (kHz)... 

SMILES (Simplified Molecular Input Line Entry Systems) is a line notation system based on principles of molecular graph theory for entering and representing molecules and reactions in computer (10-13). It uses a set of simple specification rules to derive a SMILES string for a given molecular structure (or more precisely, a molecular graph). A simplified set of rules is as follows ... 

Computer-Aided Property Estimation Computer-aided structure estimation requires the structure of the chemical compounds to be encoded in a computer-readable language. Computers most efficiently process linear strings of data, and hence linear notation systems were developed for chemical structure representation. Several such systems have been described in the literature. SMILES, the Simplified Molecular Input Line Entry System, by Weininger and collaborators [2-4], has found wide acceptance and is being used in the Toolkit. Here, only a brief summary of SMILES rules is given. A more detailed description, together with a tutorial and examples, is given in Appendix A. 

The Simplified Molecular Input Line Entry System (SMILES) is frequently used for computer-aided evaluation of molecular structures [1-3]. SMILES is widely accepted and computationally efficient because SMILES uses atomic symbols and a set of intuitive rules. Before presenting examples, the basic rules needed to enter molecular structures as SMILES notation are given. 

In addition to these publications, software is available that allows the user to determine vapor pressures of a wide variety of compounds at room temperature. The Texas Research Center (TRC) (1996) distributes a PC DOS/Windows database that contains experimentally derived Antoine constants for approximately 6000 chemicals from which vapor pressures at user-selected temperatures can be calculated. Another Windows-based program, MPBPVP by Meylan and Howard (1996), estimates the vapor pressure of organic compounds from their SMILES (Simplified Molecular Input Line Entry System) structure and their boiling points using the Antoine equation, the Grain-Watson method, and the Mackay method. 

Registry of Toxic Effects of Chemicals (Sub-)Structural Alerts Statistical Analysis System Aqueous solubility Structure-Activity Relationship Self-Consistent Field Structure Data File Sex Hormone Binding Globulin Simplified Molecular Line Entry System... 

In order to calculate a physicochemical property, the structure of a molecule must be entered in some manner into an algorithm. Chemical structure notations for input of molecules into calculation software are described in Chapter 2, Section VII and may be considered as either being a 2D string, a 2D representation of the structure, or (very occasionally) a 3D representation of the structure. Of this variety of methods, the simplicity and elegance of the 2D linear molecular representation known as the Simplified Molecular Line Entry System (SMILES) stands out. Many of the packages that calculate physicochemical descriptors use the SMILES chemical notation system, or some variant of it, as the means of structure input. The use of SMILES is well described in Chapter 2, Section VII.B, and by Weininger (1988). There is also an excellent tutorial on the use of SMILES at www.daylight.com/dayhtml/smiles/smiles-intro.html. 

Devillers et al. (1996) have commented that most QSARs for the prediction of BCF perform similarly up to log Kow 6. In view of the fact that the computer program BCFWIN version 2.14 is freely available from the EPA website (www.epa.gov/oppt/exposure/docs/episuitedl.htm), it is recommended that this be used for BCF prediction for chemicals with log < 6 the proviso is that highly reactive chemicals will probably have a higher than predicted BCF, perhaps by up to two orders of magnitude. BCFWIN requires that the chemical structure be input using Simplified Molecular Line Entry System (SMILES) notation (Weininger, 1988) or as a Chemical Abstracts Service (CAS) number. 

The most commonly used identifiers today include line notation identifiers (e.g., Simplified Molecular Input Line Entry System [SMILES] and International Chemical Identifier [InChls]), tabular identifiers (e.g., Molfile and Structure Definition [SD] file types), and portable mark-up language identifiers (e.g., Chemical Markup Language [CML] and FlexMol). Each identifier has its strengths and weaknesses as detailed in Chapter 5. Chapters 5 and 6 provide enough information to guide researchers in choosing the most appropriate formats for their individual use. 

Chemical structure representation formats (e.g., InChl, Simplified Molecular Line Entry System [SMILES])... 

Process step definition Functional performance criteria Functional failure mode analysis Failure mode recovery requirements Informational requirements Information structures Legacy system interfaces Data entry range Data retention requirements Human/machine interface requirements Screen specifications Data entry modes Refresh rates Data migration... 

WEN and SMILES fragments correspond respectively to substrings of the Wiswesser Line Notation or Simplified Molecular Input Line Entry System strings used for encoding the chemical structures. Since simple... 

Because of the great variation in the details of POTW design and equipment, use of standardized data entry screens might have proved confusing to users, and would have resulted in the collection of superfluous data (both slowing system operation and taxing the memory limitations of our delivery platform). The object-oriented knowledge representation structure made possible by ALEX and Smalltalk have allowed us to implement a very flexible data entry system matched specifically to the individual POTW under analysis. An "explain" facility is available for all data requested, and default values may be used if a user is unable to provide selected plant information. 

SMILES (Simplified Molecular Input Line Entry System) was invented by Weininger5 to facilitate the representation and manipulation of molecular structures using computers. It uses standard atomic symbols to represent atoms and the symbols - for single bond, = for double bond, and for triple bond. Hydrogen atoms can be represented explicitly but are almost always represented implicitly using normal conventions of valence bond theory. Single bonds need not be explicitly written. For example, propane is C-C-C or simply CCC. Methylamine is CN, and C N is hydrogen cyanide. Propene is C=CC. For more complex structures with branched bonds, parentheses are used. For example, CC(C)0 is isopropyl alcohol, whereas CCCO is propanol. 

Simplified Molecular Input Line Entry System (SMILES) is a simple, yet complete description of molecular structure that considers the atoms and bonds in a molecule. Using unique canonical SMILES, an indexed table lookup of a structure can be quickly done. For example, the SQL to lookup phenol is ... 

The use of Simplified Molecular Input Line Entry System (SMILES) as a string representation of chemical structure makes possible much of what has been discussed in earlier chapters of this book. A chemical reaction could be represented as a collection of SMILES, some identified as reactants and some as products. It is possible to define a table to do this, or perhaps use some arrays of character data types, but a syntax extension of standard SMILES allows reaction to be expressed easily. SMIRKS is an extension of SMILES and SMiles ARbitrary Target Specification (SMARTS). It is used to represent chemical transformations. SMIRKS can also be used in a transformation function to combine SMILES reactants to produce SMILES products. 

The UM-BBD-PPS predicts all possible metabolic pathways based on its metabolic rules [10]. The user draws a structure or enters a SMILES (Simplified Molecular Input Line Entry System) string representing the compound of interest. The PPS identifies funcfional groups and matches them to appropriate rules. First-round metabolites are produced. Any first-round metabolite can be selected, and used to match another set of rules. When no metabolic rules are matched, the cycle is stopped. This could indicate a non-metabolizable compound or, in other cases, it is an endpoint metabolite that is a common intermediary compound. 

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