MACCS system development

Nuclear Magnetic Resonance Spectroscopy. Bmker s database, designed for use with its spectrophotometers, contains 20,000 C-nmr and H-nmr, as weU as a combined nmr-ms database (66). Sadder Laboratories markets a PC-based system that can search its coUection of 30,000 C-nmr spectra by substmcture as weU as by peak assignments and by fiiU spectmm (64). Other databases include one by Varian and a CD-ROM system containing polymer spectra produced by Tsukuba University, Japan. CSEARCH, a system developed at the University of Vieima by Robien, searches a database of almost 16,000 C-nmr. Molecular Design Limited (MDL) has adapted the Robien database to be searched in the MACCS and ISIS graphical display and search environment (63). Projects are under way to link the MDL system with the Sadder Hbrary and its unique search capabiHties. 

Several commercial providers of chemoinformatic tools have issued systems for calculating molecular fingerprints. Commonly used formats are those used in the molecular structure database systems developed by MDL (ISIS and MACCS) and the Daylight fingerprints. 

MACCS, originally developed by MDL information systems, now part of Accelrys, San Deigo, California. 

While end user chemists had never been involved in our in-house chemical database development, when it became practical to look at graphics alternatives, they were an integral part of the decisionmaking. A task force of information specialists, systems analysts, and chemists evaluated the course of action whether to build a graphics system in-house, or to buy existing software. Economic factors continued to prevail, and it was seen that in-house development, however much preferred from a customization standpoint, would take too long to complete. The result of several months of discussion, demonstrations and site visits, was the decision to license Molecular Design Ltd. s MACCS system, the now well-known molecular connectivity-based retrieval system. 

Twenty years is a relatively long time for a custom in-house-developed system of this type to survive. This is particularly true since viable commercial chemical database software came into existence in the late 1970s in the form of the MACCS system, which was widely adopted by industry, but the object of a great deal of user dissatisfaction. Cousin was regularly reviewed by both inside and outside reviewers against other available systems and remained the recommended choice. We believe that some of the reasons for this longevity were the following ... 

MACCS (Molecular ACCess System), developed and distributed by MDL Information Systems, San Leandro, CA. This older system is being augmented with ISIS (Ref. 23). 

The SDF structure file is used for delivery to hosts and in-house customers of the Beilstein structure file. Other delivery formats produced by the registry software include Tel6systemes-DARC and MDL MOLfile formats. Large DARC and MOLfile structure files have been created at the Beilstein Institute for the purpose of benchmarking the DARC-SMS and MDL MACCS-II substructure search systems against the S4 substructure search system developed jointly by the Beilstein Institute and the software house Softron GmbH . 

Since 1986, others have developed their own speciaUsed 3-D searching systems. These systems include the ALADDIN system developed at Abbott, the 3DSEARCH system developed at Lederle, and the MACCS-3D system developed by Molecular Design Limited in collaboration with an industrial consortium. Any one of these systems can be used to develop synthetic targets using the strategy outlined above. 

MACCS-II enables direct interface with other database management systems, such as the Relational Database Management System (RDBMS) and Oracle, so that databases which contain text and numeric data for which special interfaces are normally needed can be constmcted. Eor example, an Oracle MACCS-II linked system is currendy being used by the National Institute on Dmg Abuse (113) to develop a database that will allow scientists to determine the molecular stmctures of cocaine and other controlled substances as well as designer dmgs. 

MACCS-II Drug Data Report is available from MDL Information Systems Inc., San Leandro, CA 94577 and contains biologically active compounds in the early stages of drug development. 

A VAX environment was chosen for the development of the CHESS system for a number of reasons (Figure 8). First is the belief that small computers, such as PC s, do not offer the resources necessary to construct moderate to large scale expert system. Once developed, however, some systems may be ported to smaller computers. Another important reason is that MACCS is VAX based. GUESS was also originally written in a VAX environment. 

For chemical reaction literature, chemists use the SYNLIB database from Distributed Chemical Graphics. SYNLIB is a well-documented, user-friendly system, designed for end user browsing. Figure 6 shows sample SYNLIB printed output, two records to the page. For chemical supplier information, the Fine Chemicals Directory from Fraser Williams (Scientific Systems) Ltd. is available through MACCS, as is an internally developed database of chemicals available in our Chemical Stockroom. 

By 1986, when we were ready to buy chemical structure software, there was a number of systems on offer. A year earlier the position might have been very different. The main contenders were MACCS, DARC and OSAC, a program derived from the reaction storage and searching program, ORAC. In addition, HTSS and SABRE were of interest although we had doubts about their state of development at the time. 

A feature of the SOCRATES connection table design that merits special mention is our inclusion of aromatic bonds thus an algorithm has been developed for detecting all aromatic bonds in a ring or ring system which more closely accords with the chemists concept of aromaticity than that found in other systems (e.g., MACCS does not consider... 

ChemSketch is a software program developed in-house to draw chemical structures and to retrieve structures from MACCS. It is written in VAX C and will run on any of the VAX CPUs as long as they are running the VMS operating system. ChemSketch currently supports Tektronix 401x, VT-640, and VT-240 terminal emulation. 

By 1984, the use of chemical database systems was well understood and wide-spread in the chemical/pharmaceutical industry. Their use provided researchers with rapid access to company-wide, and in some cases industry-wide, chemical information. A few companies had developed proprietary systems for this purpose such as Upjohn s COUSIN and ICFs CROSSBOW. However, most companies were using commercial chemical database systems such as Molecular Design s (MDL s) MACCS. ... 

Much of this report discusses the MACCS-II program. That project was managed by the author who gratefully acknowledges the contributions of the development team. Team members included R. Briggs Jr., R. Greenberg, G. Hazen, J. Mikesell, D. Pirkle, D. Raich, B. Reid, S. Shaw, R. Shier, M. Van Duyne and B. Van Vliet. The team in turn thanks the many people in the chemical/pharmaceutical industry and at MDL who contributed to the development of this chemical-scientific database system. 

MACCS (Molecidar ACCess System), 1989, developed and distributed by Molecular Design Ltd, San Leandro, Califomia, U.S.A. 

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