Campus Units

Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of, Baker Center for Bioinformatics and Biological Statistics

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

5-14-2010

Journal or Book Title

Biochemistry

Volume

49

Issue

27

First Page

5683

Last Page

5704

DOI

10.1021/bi100110x

Abstract

It was found that the variety of function-related conformational changes (“movements”) in proteins is beyond the earlier simple classifications. Here we offer biochemists a more comprehensive, transparent and easy to use approach allowing a detailed and accurate interpretation of such conformational changes. It makes possible a more multifaceted characterization of protein flexibility by identifying rigidly and non-rigidly repositioned fragments, stable and non-stable fragments, domain and non-domain repositioning. “Coordinate uncertainty thresholds” derived from computed differences between independently determined coordinates of the same molecules are used as the criteria for conformational identity. ‘Identical’ rigid substructures are localized in the distance difference matrices (DDMs). A sequence of simple transformations determines whether a structural change occurs by rigid body “movements” of fragments or largely through non-rigid-body deformations. We estimate the stability of protein fragments and compare stable and rigidly moving fragments. The motions computed with the coarse-grained elastic networks are also compared to their DDM analogs. We study and suggest a classification for 17 structural pairs, differing in their functional states. For 5 of the 17 proteins conformational change cannot be accomplished by rigid-body transformations, and require significant non-rigid body deformations. Stable fragments rarely coincide with rigidly moving fragments, and often disagree with the CATH identifications of domains. Almost all monomeric apo-chains, containing stable fragments/domains, indicate instability of the entire molecule, suggesting the importance of fragments and domains motions prior to stabilization by substrate binding or crystallization. Notably kinases exhibit the greatest extent of non-rigidity among the proteins investigated.

Comments

This is a manuscript of an article published as Rashin, Alexander A., Abraham HL Rashin, and Robert L. Jernigan. "Diversity of function-related conformational changes in proteins: coordinate uncertainty, fragment rigidity, and stability." Biochemistry 49, no. 27 (2010): 5683-5704. doi:10.1021/bi100110x. Posted with permission.

Copyright Owner

American Chemical Society

Language

en

File Format

application/pdf

Published Version

Share

COinS