Protein docking using spherical polar Fourier correlations

Abstract

We present a new computational method of docking pairs of proteins by using spherical polar Fourier correlations to accelerate the search for candidate low-energy conformations. Interaction energies are estimated using a hydrophobic excluded volume model derived from the notion of "overlapping surface skins," augmented by a rigorous but "soft" model of electrostatic complementarity. This approach has several advantages over former three-dimensional grid-based fast Fourier transform (FFT) docking correlation methods even though there is no analogue to the FFT in a spherical polar representation. For example, a complete search over all six rigid-body degrees of freedom can be performed by rotating and translating only the initial expansion coefficients, many unfeasible orientations may be eliminated rapidly using only low-resolution terms, and the correlations are easily localized around known binding epitopes when this knowledge is available. Typical execution times on a single processor workstation range from 2 hours for a global search (5 x 10(8) trial orientations) to a few minutes for a local search (over 6 x 10(7) orientations). The method is illustrated with several domain dimer and enzyme-inhibitor complexes and 20 large antibody-antigen complexes, using both the bound and (when available) unbound subunits. The correct conformation of the complex is frequently identified when docking bound subunits, and a good docking orientation is ranked within the top 20 in 11 out of 18 cases when starting from unbound subunits. Proteins 2000;39:178-194.

Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells

“…Models of the N-terminal regions of Als1 and Als3 generated as above were then examined for predicted interactions with E-cadherin or N-cadherin [62] in silico using the program Hex 4.5 [63,64]. The structures of these cadherins have been determined to a resolution of 2 Å by x-ray crystallography [45].…”

Neuronal porosome – The secretory portal at the nerve terminal: Its structure–function, composition, and reconstitution

“…Immuno-AFM, immuno–EM, single particle cryo-EM tomography (Zang and Ren 2012), and SAXS studies on isolated neuronal porosomes will help determine the distribution of some of the major proteins within the complex. Computational approaches employing coarse-grain molecular docking studies (Gray et al, 2003a; Smith and Sternberg, 2002; Janin et al, 2003; Schneidman-Duhovny et al, 2003; Katchalski-Katzir et al, 1992; Gabb et al, 1997; Moont and Sternberg 2002; Jackson et al, 1998; Vakser 1995; Mandell et al, 2001; Chen and Weng 2003; Ritchie and Kemp 2000; Fernandez-Recio et al, 2002; Grey et al, 2003b; Gabdoulline and Wade 2001; Fitzjohn and Bates 2003), homology modeled interactions (Aloy et al, 2004; Pieper et al, 2004; Marti-Renom et al, 2000), and fitting of known atomic structures of protein-protein interactions and complexes (Volkmann et al, 2000; Roseman 2000; Wriggers and Birmanns 2001; Ceulemans and Russell 2004; Volkmann and Hanein 1999; Rossmann et al, 2001; Chiu et al, 2002; Chacon and Wriggers 2002), will further understanding of the molecular structure of the neuronal porosome complex. Such ultrastructural and mass spectrometry methods will provide complementary information and the high degree of cross-validation required to build an accurate structural model of this complex organelle, -the neuronal porosome complex.…”

Protein-Protein Interface Detection Using the Energy Centrality Relationship (ECR) Characteristic of Proteins

“…Our preliminary attempts at this look promising. As a proof of concept, we filtered the top 500 scoring poses generated by the docking program Hex [53] with ECR for several Enzymes and Antibody-HL interactions (1tzi_AB, 1bsr_AB, 1bsl_AB, 1biq_AB). In all these, we were able to identify the lowest RMSD pose and in one case, 1bsr_AB, were able to identify a lower RMSD pose than Hex.…”