Low-resolution docking: Prediction of complexes for underdetermined structures

✍ Scribed by Ilya A. Vakser

• Publisher: Wiley (John Wiley & Sons)
• Year: 1998
• Tongue: English
• Weight: 950 KB
• Volume: 39
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/(sici)1097-0282(199609)39:3<455::aid-bip16>3.0.co;2-a

✦ Synopsis

Prediction of Complexes for Underdetermined Structures

One of the mo.st,fiindamental questions concerning ligand-receptor interaction is whether such a proce.rs of intermolecular association is generally determined by local structural elements of the purl icipating moiecules, or whether there are also iarge-scale motifi in molecule structures that facilitate complex formation. From the point of view of practical docking computations, the elaborate character of local structural details in ligand-receptor interaction creates a large number oflfalse-positive matches, which intefere with determination of the best fit. Another signiJicant obstacle in protein docking is the problem of structtiral data inaccuracy (poor structure resolution, conformational changes upon complex formation, etc.) . Our study Protein Eng., 8, 371-3771, based on ultralow (-I k resolution) representation of molecular structures, allowes to average all high-resolution structural details, and still predict most ofthe structiiral features ofthe ligand-receptor complex. The approach dramatically improves the signal-to-noise ratio in determination of the best f i t , and moves the structure inaccuracy tolerance to the range of the macrostructure. In the present paper, we describe a,further validation ofthe main principles ofthis approach and a detailed analysis of the low-resolution docking results. This includes clustering of ligand positions around the receptor molecule and cross-validation ofligands and receptors from different complexes. We also discuss the important implications of the approach to the multiple-minima problem and a possible role ofdiferent structural elements in the recognition mechanism.