Premium
Amplitudes and directions of internal protein motions from a JAM analysis of 15 N relaxation data
Author(s) -
Kitao Akio,
Wagner Gerhard
Publication year - 2006
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.1839
Subject(s) - chemistry , relaxation (psychology) , amplitude , maxima and minima , molecular dynamics , resonance (particle physics) , protein dynamics , nuclear magnetic resonance , computational chemistry , molecular physics , atomic physics , physics , mathematical analysis , quantum mechanics , psychology , social psychology , mathematics
A method has been developed for characterizing dynamic structures of proteins in solution by using nuclear magnetic resonance (NMR) restraints and 15 N relaxation data. This method is based on the concept of the jumping‐among‐minima (JAM) model. In this model we assume that protein dynamics can be described on the basis of conformational substates, and involves intra‐ and inter‐substate motion. A set of substates is created by picking energy‐minimized conformations from the conformational space consistent with the geometric NMR restraints. Intra‐substate motions, which occur on the timescale of ∼10 ps, are simulated with molecular dynamics (MD) calculations with force‐field energy terms. Statistical weights of the conformational substates are determined to reproduce the NMR relaxation parameters. The refinement procedure consists of four stages: (i) determination of the ensemble of structures that satisfy NMR restraints, (ii) determination of intra‐substate fluctuation, (iii) determination of statistical weights of conformational substates to reproduce model‐free relaxation parameters, and (iv) analysis of the resulting dynamic structure to determine amplitudes and directions of internal protein motions. This method was employed to investigate structure and dynamics of the adhesion domain of human CD2 (hCD2) in solution. Two major collective modes, whose contributions to atomic mean‐square fluctuations are 77.1% in total, are identified by the refinement. The first mode is interpreted as a rigid‐body motion of a protein segment consisting of a part of the BC loop, a part of the F strand, and the FG loop. Another type of smaller‐amplitude mode is indicated for the C′C″ loop. The motions affect primarily the curvature of the slightly concave counterreceptor‐binding site and represent transitions between a concave (closed) and flat (open) binding face. By comparing the ensemble of structures in solution to the complex structure with counterreceptor CD58, we found that these two types of motions resemble the change upon counterreceptor binding. Copyright © 2006 John Wiley & Sons, Ltd.