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Geometric and chemical patterns of interaction in protein–ligand complexes and their application in docking
Author(s) -
Moreno Ernesto,
León Kalet
Publication year - 2002
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10026
Subject(s) - dock , template , docking (animal) , ligand (biochemistry) , protein data bank , chemistry , amino acid residue , amino acid , searching the conformational space for docking , protein–ligand docking , representation (politics) , protein ligand , stereochemistry , protein structure , binding site , biological system , computer science , computational chemistry , peptide sequence , molecular dynamics , receptor , biology , biochemistry , virtual screening , medicine , nursing , politics , political science , law , gene , programming language
We present a new method for representing the binding site of a protein receptor that allows the use of the DOCK approach to screen large ensembles of receptor conformations for ligand binding. The site points are constructed from templates of what we called “attached points” (ATPTS). Each template (one for each type of amino acid) is composed of a set of representative points that are attached to side‐chain and backbone atoms through internal coordinates, carry chemical information about their parent atoms and are intended to cover positions that might be occupied by ligand atoms when complexed to the protein. This method is completely automatic and proved to be extremely fast. With the aim of obtaining an experimental basis for this approach, the Protein Data Bank was searched for proteins in complex with small molecules, to study the geometry of the interactions between the different types of protein residues and the different types of ligand atoms. As a result, well‐defined patterns of interaction were obtained for most amino acids. These patterns were then used for constructing a set of templates of attached points, which constitute the core of the ATPTS approach. The quality of the ATPTS representation was demonstrated by using this method, in combination with the DOCK matching and orientation algorithms, to generate correct ligand orientations for >1000 protein–ligand complexes. Proteins 2002;47:1–13. © 2002 Wiley‐Liss, Inc.