Evaluation of GRAMM low-resolution docking methodology on the hemagglutinin-antibody complex

Abstract

A single protein–protein pair, the complex of the influenza virus hemagglutinin with an antibody (Fab BH151), was suggested for prediction at the second experiment on the Critical Assessment of Techniques for Protein Structure Prediction. To predict the structure of the complex, we applied our docking program GRAMM at a decreased resolution (to accommodate the conformational inaccuracies). The lowest‐energy match showed a remarkable “low‐resolution” surface complementarity between the molecular structures. After receiving the experimental structure of the complex we had a chance to verify our assumptions and results. The analysis of the hemagglutinin–antibody interface revealed several significant conformational changes in the side chains, which resulted in deep interpenetrations of the hemagglutinin and the antibody structures. This confirmed our initial assumption that the structural changes will be beyond the tolerance of high‐resolution rigid‐body docking. The comparison of the predicted low‐resolution match, submitted as the solution, and the experimentally determined complex showed significant structural discrepancies in the orientation of the antibody, due to the low‐resolution character of the docking. Because of the severe structural errors, no residue–residue contacts were predicted correctly. However, a significant part of the antigenic site was determined. This illustrates the practical value of the present methodology for the initial prediction of the binding site, as well as points out the problem of transition from the low‐resolution predictions of protein–protein complexes to the accurate structure. Proteins, Suppl. 1:226–230, 1997. © 1998 Wiley‐Liss, Inc.

All-Atom Monte Carlo Approach to Protein–Peptide Binding

“…9,10), including programs such as AutoDock, 11 DOCK, 12 and GRAMM. 13 By contrast, few methods have been developed for protein-peptide interactions specifically. [14][15][16][17][18] This is likely, in part, due to the inherent flexibility of the peptide chain, which makes simulations of protein-peptide binding a highly nontrivial task.…”

Docking unbound proteins using shape complementarity, desolvation, and electrostatics

“…A few algorithms are capable of searching the entire 6‐dimensional (6‐D) rotational and translational space of the ligand. Notably, Fast Fourier Transform (FFT) based methods19–22 performed well in two blind trials 18, 23, 24. Others include an algorithm that matches surface cubes,25 a computer‐vision‐based algorithm,26 a method based on Boolean operations,27 and a method based on spherical polar Fourier correlations 28.…”

The structural insights of stem cell factor receptor (c-Kit) interaction with tyrosine phosphatase-2 (Shp-2): An in silico analysis

“…3). These repulsion values in A° were determined by three factors, r ij (distance between ligand and receptor), U (energy of repulsion) and R, "range" of the potential (the grid step) using the mathematical relationship [29,30], as shown in the Additional file 5. Distances lesser than 10A°, between important residues (within the predicted interactive zones), decided the best positioning of two proteins for further analysis (Fig.…”