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Principles of docking: An overview of search algorithms and a guide to scoring functions
Author(s) -
Halperin Inbal,
Ma Buyong,
Wolfson Haim,
Nussinov Ruth
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.10115
Subject(s) - docking (animal) , searching the conformational space for docking , macromolecular docking , computer science , protein–ligand docking , protein folding , computational biology , artificial intelligence , algorithm , protein structure , virtual screening , molecular dynamics , chemistry , biology , computational chemistry , medicine , biochemistry , nursing
The docking field has come of age. The time is ripe to present the principles of docking, reviewing the current state of the field. Two reasons are largely responsible for the maturity of the computational docking area. First, the early optimism that the very presence of the “correct” native conformation within the list of predicted docked conformations signals a near solution to the docking problem, has been replaced by the stark realization of the extreme difficulty of the next scoring/ranking step. Second, in the last couple of years more realistic approaches to handling molecular flexibility in docking schemes have emerged. As in folding, these derive from concepts abstracted from statistical mechanics, namely, populations. Docking and folding are interrelated. From the purely physical standpoint, binding and folding are analogous processes, with similar underlying principles. Computationally, the tools developed for docking will be tremendously useful for folding. For large, multidomain proteins, domain docking is probably the only rational way, mimicking the hierarchical nature of protein folding. The complexity of the problem is huge. Here we divide the computational docking problem into its two separate components. As in folding, solving the docking problem involves efficient search (and matching) algorithms, which cover the relevant conformational space, and selective scoring functions, which are both efficient and effectively discriminate between native and non‐native solutions. It is universally recognized that docking of drugs is immensely important. However, protein–protein docking is equally so, relating to recognition, cellular pathways, and macromolecular assemblies. Proteins function when they are bound to other molecules. Consequently, we present the review from both the computational and the biological points of view. Although large, it covers only partially the extensive body of literature, relating to small (drug) and to large protein–protein molecule docking, to rigid and to flexible. Unfortunately, when reviewing these, a major difficulty in assessing the results is the non‐uniformity in the formats in which they are presented in the literature. Consequently, we further propose a way to rectify it here. Proteins 2002;47:409–443. © 2002 Wiley‐Liss, Inc.