Title:

DNA COMPUTING

Area of Topic:- An increasing amount of 3D information is making its way onto the Web and
into corporate databases. Because of this, users need ways to store, index, and search this information.

Abstract:In todays information oriented world where the speed of processing and storage capacity have become the governing factors, the conventional silicon computers to some extent have tried to keep up with the growing needs for faster processing speeds and larger data storage capacity. This imperative job will be taken up by DNA Computers in the near future which will revolutionize the computer field and the associated fields in a way which was not possible before. These computers when operational will have ability to perform billions of operations in a single second and the capacity to store immense amount of data. As the name DNA Computer implies these computers use DNA as the basic storage and processing element and are the latest developments in the field of bioinformatics.

Introduction
Although serendipity has played an important role in drug discovery [1], computers now are crucial to the rational design of new medicinal agents. The goal of modern computer-aided drug design (CADD) is to make use of statistical and molecular modeling techniques to aid in the design or discovery of new lead structures. It is hoped that computers will help reduce the staggering costs in time and resources that are required to get a new drug to market. The availability of rapid, approximate molecular modeling techniques allow organizations to generate

3D versions of large corporate structural databases with hundreds of thousands of entries [2]. The recent techniques for studying 3D structure-activity relationships (3D-SAR) combine statistical and molecular modeling approaches leading to the generation of very large data arrays [3], which can be managed by chemical structural databases. Furthermore, this technology is being increasingly used by synthetic chemists with little statistical or molecular modeling backgrounds. The current emphasis in CADD is on lead development, which contrasts with early efforts that concentrated on lead optimization. Techniques for the latter are well-established, while techniques for lead development are still under development and generally involve either (a) using computer technology to propose a new structure to fit a putative or known receptor (de novo design), or (b) searching a database of known structures for those with a desired activity or similarity to active compounds. The latter approach is more widely practiced due to several advantages: (1) Available drugs may already have toxicity and distribution profiles established; (2) the approach makes optimal use of existing resources; and finally, (3) computer software is readily available and does not require modeling expertise to be used effectively. Along with statistical and molecular modeling tools, 3D structural databases have become a key element in modern 3D CADD. This paper describes some 3D searching applications using the ISIS/3D chemical information management system [4]. We should note that the main purpose of 3D searching is to locate potential structures that can fit into a given receptor. Toward this goal, the techniques described in this paper involve developing and optimizing a 3D search query against a database of known compounds. Once an optimum query is obtained (by optimum we mean hitting as many of the active compounds as possible with the fewest possible inactive ones), this query can then be used to search databases of compounds with unknown activities. The resultant hit list will conceivably have a similar percentage of active compounds (or quality leads) as those obtained from searching a database with compounds of known activities.

Literature survey review of prior work

3D SEARCHING An increasing amount of 3D information is making its way onto the Web and into corporate databases. Because of this, users need ways to store, index, and search this information. Typical

Websearching approaches, such as Google's, can't do this. Even for 2D images, they generally search only the textual parts of a file, noted Greg Notess, editor of theonline Search Engine Showdown newsletter. However, researchers at universities such as Purdue and Princeton have begun developing search engines that can mine catalogs of 3D objects, such as airplane parts, by looking for physical, not textual, attributes. Users formulate a query by using a drawing application to sketch what they are looking for or by selecting a similar object from a catalog of images. The search engine then finds the items they want.The company must make it again, wasting valuable time and money 3D SEARCHING Advances in computing power combined with interactive modeling software , which lets users create images as queries for searches, have made 3Dsearch technology possible. Methodology used involves the following steps " Query formulation " Search process "Search result QUERY FORMULATION True 3D search systems offer two principal ways to formulate a query: Users can select objects from a catalog of images based on product groupings, such as gears or sofas; or they can utilize adrawing program to create a picture of the object they are looking for. or example, Princeton's 3D search engine uses an application to let users draw a 2D or 3D representation of the object they want to find. The above picture shows the query interface of a 3D search system. SEARCH PROCESS The 3Dsearch system uses algorithms to convert the selected or drawn image-based query into a mathematical model that describes the features of the object being sought. This converts drawings and objects into a form that computers can work with. The search system then compares the mathematical description of the drawn or selected object to those of 3D objects stored in a database, looking for similarities in the described features. The key to the way computer programs look for 3D objects is the voxel (volume pixel). A voxel is a set of graphical data-such as position, color, and density-that defines the smallest cubeshaped building block of a 3D image. Computers can display 3D images only in two dimensions. To do this,3D rendering software takes an object and slices it into 2D cross sections. The cross sections consist of pixels (picture elements), which are single points in a 2D image. To render the 3D image on a 2D screen, the computer determines how to display the 2D cross sections stacked on top of each other, using the applicable interpixel and interslice distances to position them properly. The computer interpolates data to fill in interslice gaps and create a solid image.

Topic Description:Definition
From computer-aided design (CAD) drawings of complex engineering parts to digital representations of proteins and complex molecules, an increasing amount of 3D information is making its way onto the Web and into corporate databases. Because of this, users need ways to store, index, and search this information. Typical Websearching approaches, such as Googles, cant do this. Even for 2D images, they generally search only the textual parts of a file, noted Greg Notes, editor of the online Search Engine Showdown newsletter. However, researchers at universities such as Purdue and Princeton have begun developing search engines that can mine catalogs of 3D objects, such as airplane parts, by looking for physical, not textual, attributes. Users formulate a query by using a drawing application to sketch what they are looking for or by selecting a similar object from a catalog of images. The search engine then finds the items they want. The company must make it again, wasting valuable time and money 3D SEARCHING Advances in computing power combined with interactive modeling software, which lets users create images as queries for searches, have made 3Dsearch technology possible. Methodology used involves the following steps Queryformulation Searchprocess Search result QUERY FORMULATION

True 3D search systems offer two principal ways to formulate a query: Users can select objects from a catalog of images based on product groupings, such as gears or sofas; or they can use a

drawing program to create a picture of the object they are looking for. or example, Princetons 3D search engine uses an application to let users draw a 2D or 3D representation of the object they want to find. The above picture shows the query interface of a 3D search system. SEARCH PROCESS

The 3D-search system uses algorithms to convert the selected or drawn image-based query into a mathematical model that describes the features of the object being sought. This converts drawings and objects into a form that computers can work with. The search system then compares the mathematical description of the drawn or selected object to those of 3D objects stored in a database, looking for similarities in the described features. The key to the way computer programs look for 3D objects is the voxel (volume pixel). A voxel is a set of graphical data-such as position, color, and density-that defines the smallest cup-shaped building block of a 3D image. Computers can display 3D images only in two dimensions. To do this, 3D rendering software takes an object and slices it into 2D cross sections. The cross sections consist of pixels (picture elements), which are single points in a 2D image. To make the 3D image on a 2D screen, the computer determines how to display the 2D cross sections stacked on top of each other, using the applicable interpixel and interstice distances to put them properly. The computer interpolated facts to fill in interstice gaps and create a solid image.

Detail description:Although serendipity has played an important role in drug discovery [1], computers now are crucial to the rational design of new medicinal agents. The goal of modern computer-aided drug design (CADD) is to make use of statistical and molecular modeling techniques to aid in the design or discovery of new lead structures. It is hoped that computers will help reduce the

staggering costs in time and resources that are required to get a new drug to market. The availability of rapid, approximate molecular modeling techniques allow organizations to generate 3D versions of large corporate structural databases with hundreds of thousands of entries [2]. The recent techniques for studying 3D structure-activity relationships (3D-SAR) combine statistical and molecular modeling approaches leading to the generation of very large data arrays [3], which can be managed by chemical structural databases. Furthermore, this technology is being increasingly used by synthetic chemists with little statistical or molecular modeling backgrounds. The current emphasis in CADD is on lead development, which contrasts with early efforts that concentrated on lead optimization. Techniques for the latter are well-established, while techniques for lead development are still under development and generally involve either (a) using computer technology to propose a new structure to fit a putative or known receptor (de novo design), or (b) searching a database of known structures for those with a desired activity or similarity to active compounds. The latter approach is more widely practiced due to several advantages: (1) Available drugs may already have toxicity and distribution profiles established; (2) the approach makes optimal use of existing resources; and finally, (3) computer software is readily available and does not require modeling expertise to be used effectively. Along with statistical and molecular modeling tools, 3D structural databases have become a key element in modern 3D CADD. This paper describes some 3D searching applications using the ISIS/3D chemical information management system [4]. We should note that the main purpose of 3D searching is to locate potential structures that can fit into a given receptor. Toward this goal, the techniques described in this paper involve developing and optimizing a 3D search query against a database of known compounds. Once an optimum query is obtained (by optimum we mean hitting as many of the active compounds as possible with the fewest possible inactive ones), this query can then be used to search databases of compounds with unknown activities. The resultant hit list will conceivably have a similar percentage of active compounds (or quality leads) as those obtained from searching a database with compounds of known activities.

Ligand-based vs. Receptor-based 3D Searching

A key concept in 3D searching is the pharmacophore. The term, introduced by Ehrlich in the early 1900s [5], refers to the molecular framework that carries (phoros) the essential features responsible for a drug's (pharmacon) biological activity. In the current literature, the term has been expanded to refer to the 3D arrangement of functional groups that enable a compound to exert a particular biological effect. Due to stereochemical considerations (i.e., three-point attachments), many pharmacophores are defined simply in terms of three atoms and three distances. If more information is available, other geometric objects and constraints can be added, including constraints on data associated with atoms and bonds [6]. Presently, most pharmacophores are defined in terms of the atoms and bonds of the ligand structures. This ligand-based definition has advantages for input and searching purposes; in the case where the structure of the receptor is completely unknown, it is the only way one can effectively define a pharmacophore model. It is clear that drugs that bind to a common receptor do not necessarily bind with similar functional groups precisely overlapped; rather, these drugs may show multiple modes of binding [7-9]. The interactions between a drug molecule and a receptor can be dispersed and nonspecific, as in steric and lipophilic interactions - which nevertheless account for most of the free energy changes in binding [10]. Alternatively, they can be highly specific and directional, such as interactions involving H-bond donors and acceptors or those with bound metal ions. But even then, precise overlap of heteroatoms may not result, since the specific interactions occur over a range of angles, distances, and energies [11,12]. Clearly, in such cases, a receptor-based approach to a pharmacophore definition is needed to carry key features of the receptor involved in drug molecule binding. A full receptor-based pharmacophore model complements the ligand-based pharmacophore model for the same activity; it is the 'lock' for a given 'key.' This concept has been expressed and utilized previously, as in the extended molecule approach of Andrews [13]. Our purpose is to show how to implement receptor-based queries in a pharmacophore-based 3D search system. We will also evaluate the success of these queries with respect to their pharmacophoric counterparts by testing them on a database of drugs with known activities.

Methodology

THE SEARCH PROGRAM: This investigation was carried out using ISIS, chemical information management software which also provides the ability to store and search 3D structures and data. The search capabilities of ISIS/3D include data searching; exact twodimensional (2D) and 3D matching; 2D and 3D substructure searching, which may include peratom and atom-pair [6] queries; 3D 'submodel' searching, which allows matching of 3D fragments containing fixed atoms; and 3D conformationally flexible substructure (CFS) searching [14]. Combination of these types of searches allows for the construction of hybrid and flexible queries for specialized applications [15,16]. THE DATABASE: The searches were conducted in MDL Drug Data Report-3D (MDDR-3D) [17] and Comprehensive Medicinal Chemistry-3D (CMC-3D) [18] structural databases. The 94.1 release of MDDR-3D contains 47,926 3D compounds abstracted from the journal Drug Data Report, which contains information from the drug patent literature since 1988 [19]. The 3D structures were built with the CONCORD program of Pearlman [20], and a single conformation is stored in the database. QUERY DEFINITION: In ISIS/3D, queries are defined using several objects and constraints, which can be selected from a menu. Once added to a structure or query, objects and constraints can be output to standard molecule files. In general, queries will be derived either from the literature or from structures with known activity. In the first case, the 2D substructural features of the query are drawn by the user, who then adds 3D objects and constraints. In the second case, an active structure is brought into ISIS/Draw, the user prunes away the unnecessary portions of the molecule, any atom and bond types are optionally changed, and finally, any other 2D or 3D features are added to create the query. For all searches involving hydrogen or lone-pair atoms, automatic sprouting was conducted at search time, since this information is not stored in the 3D database. Sprouting used standard bond lengths, bond angles, and the perceived valency of the structure atom. The CFS searches are performed with only one difference from the default options: The maximum allowed unique mappings were increased from the default value of 5 to 99.

Application/current work in Area:-

Computer scientist Richard Lipton, at Georgia Tech, has shown how DNA computing could be used to solve NP-hard problems and the Boolean satisfiability problem, central to computing and complexity theory. Additionally, both he and Adleman have proposed DNA computing algorithms to break the Data Encryption Standard, an encryption methodology the National Security Agency developed. A group at the University of Wisconsin has been performing DNA computations on surfaces. John Reif of Duke is working on several biocomputing applications, including DNA self-assembly techniques, and using DNA as a data storage medium with an elaborate associative search methodology. Carter Bancroft at Mt. Sinai School of Medicine focuses on DNA steganography, a method of using DNA to encode hidden messages. University of Wisconsin-Madison researchers have developed a thin, gold-coated plate of glass about an inch square. They believe it is the optimum working surface on which to anchor DNA molecules. The square allows researchers to attach trillions of strands of DNA They believe that by the year 2010 the first DNA chip will be commercially available. Table 5.1: DNA Computing Research Activities Organization Focus

Bell Labs

Fabricating DNA motors for assembling electronic components

Duke University/Caltec h

Working on massively parallel addition using DNA tiles

New York University

Assembling complex nanostructures out of DNA

University of Southern California

Automating a self-contained lab system for DNA computing; proved, in theory, that DNA can crack DES data encryption standard.

Reference:
1. DNA Computing: Arrival of Biomathematics Lila Kari 2. From Microsoft to Biosoft Computing with DNA Lila Kari 3. Speeding up Computations via Molecular Biology Richard Lipton 4. Z. Frank Qie and Mi Lu Take Advantage of the Computing Power of DNA Computer