Recent Progress and Future Directions in Protein-Protein Docking

Abstract

This article gives an overview of recent progress in protein-protein docking and it identifies several directions for future research. Recent results from the CAPRI blind docking experiments show that docking algorithms are steadily improving in both reliability and accuracy. Current docking algorithms employ a range of efficient search and scoring strategies, including e.g. fast Fourier transform correlations, geometric hashing, and Monte Carlo techniques. These approaches can often produce a relatively small list of up to a few thousand orientations, amongst which a near-native binding mode is often observed. However, despite the use of improved scoring functions which typically include models of desolvation, hydrophobicity, and electrostatics, current algorithms still have difficulty in identifying the correct solution from the list of false positives, or decoys. Nonetheless, significant progress is being made through better use of bioinformatics, biochemical, and biophysical information such as e.g. sequence conservation analysis, protein interaction databases, alanine scanning, and NMR residual dipolar coupling restraints to help identify key binding residues. Promising new approaches to incorporate models of protein flexibility during docking are being developed, including the use of molecular dynamics snapshots, rotameric and off-rotamer searches, internal coordinate mechanics, and principal component analysis based techniques. Some investigators now use explicit solvent models in their docking protocols. Many of these approaches can be computationally intensive, although new silicon chip technologies such as programmable graphics processor units are beginning to offer competitive alternatives to conventional high performance computer systems. As cryo-EM techniques improve apace, docking NMR and X-ray protein structures into low resolution EM density maps is helping to bridge the resolution gap between these complementary techniques. The use of symmetry and fragment assembly constraints are also helping to make possible docking-based predictions of large multimeric protein complexes. In the near future, the closer integration of docking algorithms with protein interface prediction software, structural databases, and sequence analysis techniques should help produce better predictions of protein interaction networks and more accurate structural models of the fundamental molecular interactions within the cell.

Protein conformational changes induced by adsorption onto material surfaces: an important issue for biomedical applications of material science

“…The 5 protein complexes, where predictions failed, not surprisingly involved large conformational changes. As a consequence, protein flexibility is now incorporated in prediction softwares [119]. It should however be noted that besides the correct predicted structures, many incorrect ones were also generated, which undermine the usefulness of these softwares, as for now.…”

Predicting residue contacts for protein-protein interactions by integration of multiple information

“…Hence it is also needed to develop methods that can infer residue contacts: contacts between residues of two interacting proteins [8]. Docking methods are able to meet this demand, but current docking methods require a time-consuming computational process and are difficult to define the best solution [9]. In addition, the conformation changes of monomers during the formation of proteinprotein complexes are also a challenge in them [8].…”

Use of Amino Acid-Nucleotide Base Pair Potentials in Screening Protein-DNA Docked Complexes

“…Until January 5, 2013, there are over 87,000 structures deposited in the PDB (Protein Data Bank) [3], where the number of protein-NA structure is just almost 4,000. Hence, computational techniques such as protein-DNA docking will become an increasingly important way to help understand the molecular mechanisms of biological systems [4].…”

“…Until January 5, 2013, there are over 87,000 structures deposited in the PDB (Protein Data Bank) [3], where the number of protein-NA structure is just almost 4,000. Hence, computational techniques such as protein-DNA docking will become an increasingly important way to help understand the molecular mechanisms of biological systems [4].Although a number of approaches are available for predicting the docking of protein-protein, the treatment of docking of small ligands and proteins with other proteins, the treatment of the docking of nucleic acids onto proteins lags far behind [5]. Two particular problems have hampered the development of efficient docking methods: the sparsity of the information to define the DNA-binding interface and the inherent flexibility of DNA [6].…”