Thermodynamic Stability and Flexibility Characteristics of Antibody Fragment Complexes

ISSN: 1875-5305 (Online)
ISSN: 0929-8665 (Print)

Volume 24, 12 Issues, 2017

Download PDF Flyer

Protein & Peptide Letters

This journal supports open access

Aims & ScopeAbstracted/Indexed in

Submit Abstracts Online Submit Manuscripts Online

Prof. Ben M. Dunn
Department of Biochemistry and Molecular Biology
University of Florida
College of Medicine
P.O. Box 100245
Gainesville, FL

View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 1.069
5 - Year: 1.104

Thermodynamic Stability and Flexibility Characteristics of Antibody Fragment Complexes

Protein & Peptide Letters, 21(8): 752-765.

Author(s): Tong Li, Deeptak Verma, Malgorzata B. Tracka, Jose Casas-Finet, Dennis R. Livesay and Donald J Jacobs.

Affiliation: UNC Charlotte, Charlotte, NC 28223, USA.


Free energy landscapes, backbone flexibility and residue-residue couplings for being co-rigid or co-flexible are calculated from the minimal Distance Constraint Model (mDCM) on an exploratory dataset consisting of VL, scFv and Fab antibody fragments. Experimental heat capacity curves are reproduced markedly well, and an analysis of quantitative stability/flexibility relationships (QSFR) is applied to a representative VL domain and several complexes in the scFv and Fab forms. Global flexibility in the denatured ensemble typically decreases in the larger complexes due to domain-domain interfaces. Slight decreases in global flexibility also occur in the native state of the larger fragments, but with a concurrent large increase in correlated flexibility. Typically, a VL fragment has more co-rigid residue pairs when isolated compared to the scFv and Fab forms, where correlated flexibility appears upon complex formation. This context dependence on residue- residue couplings in the VL domain across length scales of a complex is consistent with the evolutionary hypothesis of antibody maturation. In comparing two scFv mutants with similar thermodynamic stability, local and long-ranged changes in backbone flexibility are observed. In the case of anti-p24 HIV-1 Fab, a variety of QSFR metrics were found to be atypical, which includes comparatively greater co-flexibility in the VH domain and less co-flexibility in the VL domain. Interestingly, this fragment is the only example of a polyspecific antibody in our dataset. Finally, the mDCM method is extended to cases where thermodynamic data is incomplete, enabling high throughput QSFR studies on large numbers of antibody fragments and their complexes.


Antibody structure, computational biology, distance constraint model, free energy landscape, and quantitative stability/ flexibility relationships.

Purchase Online Order Reprints Order Eprints Rights and Permissions

Article Details

Volume: 21
Issue Number: 8
First Page: 752
Last Page: 765
Page Count: 14
DOI: 10.2174/09298665113209990051
Price: $58
Global Biotechnology Congress 2017Drug Discovery and Therapy World Congress 2017

Related Journals

Related eBooks

Webmaster Contact: Copyright © 2017 Bentham Science