Fast approximations of the rotational diffusion tensor and their application to structural assembly of molecular complexes

We present and evaluate a rigid‐body, deterministic, molecular docking method, called ELMDOCK, that relies solely on the three‐dimensional structure of the individual components and the overall rotational diffusion tensor of the complex, obtained from nuclear spin‐relaxation measurements. We also in...

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Bibliographic Details
Published in:Proteins, structure, function, and bioinformatics structure, function, and bioinformatics, 2011-07, Vol.79 (7), p.2268-2281
Main Authors: Berlin, Konstantin, O'Leary, Dianne P., Fushman, David
Format: Article
Language:English
Subjects:
Algorithms
Binding Sites
Computational Biology - methods
Databases, Protein
Diffusion
diffusion-guided molecular assembly
ellipsoid model
ELM
Models, Molecular
PATI
Protein Binding
protein complexes
Proteins - chemistry
Proteins - metabolism
residual dipolar couplings
rigid-body docking
Rotation
Software
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Summary:We present and evaluate a rigid‐body, deterministic, molecular docking method, called ELMDOCK, that relies solely on the three‐dimensional structure of the individual components and the overall rotational diffusion tensor of the complex, obtained from nuclear spin‐relaxation measurements. We also introduce a docking method, called ELMPATIDOCK, derived from ELMDOCK and based on the new concept of combining the shape‐related restraints from rotational diffusion with those from residual dipolar couplings, along with ambiguous contact/interface‐related restraints obtained from chemical shift perturbations. ELMDOCK and ELMPATIDOCK use two novel approximations of the molecular rotational diffusion tensor that allow computationally efficient docking. We show that these approximations are accurate enough to properly dock the two components of a complex without the need to recompute the diffusion tensor at each iteration step. We analyze the accuracy, robustness, and efficiency of these methods using synthetic relaxation data for a large variety of protein‐protein complexes. We also test our method on three protein systems for which the structure of the complex and experimental relaxation data are available, and analyze the effect of flexible unstructured tails on the outcome of docking. Additionally, we describe a method for integrating the new approximation methods into the existing docking approaches that use the rotational diffusion tensor as a restraint. The results show that the proposed docking method is robust against experimental errors in the relaxation data or structural rearrangements upon complex formation and is computationally more efficient than current methods. The developed approximations are accurate enough to be used in structure refinement protocols. Proteins 2011; © 2011 Wiley‐Liss, Inc.
ISSN:0887-3585
1097-0134
DOI:10.1002/prot.23053