Conformation search rule-based

In general, five different approaches can be distinguished and are applied to explore the conformational space of a molecule systematic searches, rule-based and data-based approaches (model building), random methods, genetic algorithms, distance geometry, and simulation methods. Some of the basic principles and ideas behind these concepts have already been described in the Secs. 2 and 3 of this article. In the following, the application of these concepts to conformational analysis and searches will be discussed. 

UNITY ISIS/3D ChemDBS-3D 151 with no ring flexibility 160 with ring flexibility 122 with N = basic nitrogen 152 Systematic rule-based analysis Most suitable compounds too flexibile (>14 rotatable bonds) for systematic rule-based analysis (118 of the 122 hits from UNTTY) Searching for the 122 hits of UNITY search by Random conformational analysis 60/122 (tol = 0.5 A) 90/122 (tol = 1.0 A) Flexifit (torsional minimization) Minn (tol = 0.5 A)... 

ChemDBS-3D uses rule-based systematic conformational analysis (single = 3, alpha 4, double/conjugated = 2 points) or random rule-based (max. time 2 min), or flexifit (no VDW bump check) ISIS/3D and UNITY use torsional minimization (conformationally flexible searching and directed tweak, respectively. 

The proportions of these three conformations that exist within a complex polypeptide or protein can therefore be determined with fair accuracy (using the Chou-Fasman rules Chou and Fasman, 1974 see also Chapter 2). Results such as this protein in aqueous solution is 35% a-helical and 10% (3-structured that appear in the research literature are based on interpretation of CD spectra (Woody, 1995). A search for the particular stretches of these conformations within the polypeptide is then attempted, through deductions based on the amino-acid sequence, taking account of the locations of the hydrophilic and hydrophobic side-chains, to define the three-dimensional structure of a polypeptide. 

The last few years have seen substantial interest in the development of database-searching systems for files of 3D structures. The atom coordinate information in such databases is obtained either experimentally, usually from the Cambridge Structural Database, which contains X-ray structures that have been reported in the published literature,or by the use of a struaure-builder, which is a computer program that calculates an approximate 3D structure from a 2D connection table. - The best known of such programs is CONCORD, which uses a knowledge base of rules that describe preferred molecular conformational patterns and a simplified force-field. CONCORD has been widely used for the conversion of both in-house and public databases of 2D structures to 3D form. 

---