APEX-3D Expert System for Drug Design

Kunwar Parvez Alam CET-IILM,AHL Gr.Noida

 Apex-3D is an expert system developed to represent, elucidate, and utilize knowledge on structure-activity relationships. Apex-3D can be used to build 3D-SAR and 3D-QSAR models which can be used for activity classification and prediction. The general principle of operation is based on emulating the intelligence of a researcher engaged in establishing relationships between a compound's structural parameters and its activity.

 The corner-stone of the Apex-3D methodology is automated identification of biophores (pharmacophores) . These biophores can be used for building qualitative activity prediction rules and for creating search queries to identify new leads in a 3D-database. Identified biophores can be used as starting points for constructing 3DQSAR models when good quantitative data is available. Combination of a 3D pharmacophore with a quantitative regression equation is unique to the Apex-3D approach.

 Frame System. Apex-3D uses frames for the representation of chemical information. The notion of frames was first proposed by Marvin Minsky in the early 1970s [5]. Frames represent an object as a group of attributes. Each attribute in a particular frame is stored in a separate slot. In Apex3D, a frame system is implemented using a built-in ChemLisp language interpreter. ChemLisp represents a special dialect of the LISP language (LISt Processor) [6] widely used in artificial intelligence systems. ChemLisp accesses main data structures and modules containing basic algorithmic functions. Frames in Apex-3D are LISP expressions of the following form:

 (frame framename (type frametype) (slots ((slotname slotvalue)...))) Slots can represent variables of different types (integer, real, symbol, interval) or LISP functions used in basic algorithms. Frames are employed in Apex-3D for generating descriptors, pseudoatoms, and setting basic algorithmic parameters. Rule Management Module. Structureactivity relationships in the system are represent by means of rules that have the following form:

 Prediction of activity for novel compounds requires the biophore be present: the activity level is calculated from the QSAR equation. Description of the main functionality of modules is given below. Computational Chemistry Module. This module performs computation of the quantum-chemical and other atomic and molecular indexes. In addition it performs clustering of conformers for flexible compounds. Data Management Module. Apex-3D has an internal database system based on the RAIMA DBMS [4]. It provides storage of 3D structures, structural parameters, and activity data. Apex3D's database is interfaced with external chemical databases through files.