Unknown

Dataset Information

0

Computational and single-molecule force studies of a macro domain protein reveal a key molecular determinant for mechanical stability.


ABSTRACT: Resolving molecular determinants of mechanical stability of proteins is crucial in the rational design of advanced biomaterials for use in biomedical and nanotechnological applications. Here we present an interdisciplinary study combining bioinformatics screening, steered molecular dynamics simulations, protein engineering, and single-molecule force spectroscopy that explores the mechanical properties of a macro domain protein with mixed alpha + beta topology. The unique architecture is defined by a single seven-stranded beta-sheet in the core of the protein flanked by five alpha-helices. Unlike mechanically stable proteins studied thus far, the macro domain provides the distinct advantage of having the key load-bearing hydrogen bonds (H bonds) buried in the hydrophobic core protected from water attacks. This feature allows direct measurement of the force required to break apart the load-bearing H bonds under locally hydrophobic conditions. Steered molecular dynamics simulations predicted extremely high mechanical stability of the macro domain by using constant velocity and constant force methods. Single-molecule force spectroscopy experiments confirm the exceptional mechanical strength of the macro domain, measuring a rupture force as high as 570 pN. Furthermore, through selective deletion of shielding peptide segments, we examined the same key H bonds under hydrophilic environments in which the beta-strands are exposed to solvent and verify that the high mechanical stability of the macro domain results from excellent shielding of the load-bearing H bonds from competing water. Our study reveals that shielding water accessibility to the load-bearing strands is a critical molecular determinant for enhancing the mechanical stability of proteins.

SUBMITTER: Guzman DL 

PROVIDER: S-EPMC2836608 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Computational and single-molecule force studies of a macro domain protein reveal a key molecular determinant for mechanical stability.

Guzmán Dora L DL   Randall Arlo A   Baldi Pierre P   Guan Zhibin Z  

Proceedings of the National Academy of Sciences of the United States of America 20100113 5


Resolving molecular determinants of mechanical stability of proteins is crucial in the rational design of advanced biomaterials for use in biomedical and nanotechnological applications. Here we present an interdisciplinary study combining bioinformatics screening, steered molecular dynamics simulations, protein engineering, and single-molecule force spectroscopy that explores the mechanical properties of a macro domain protein with mixed alpha + beta topology. The unique architecture is defined  ...[more]

Similar Datasets

| S-EPMC3059573 | biostudies-literature
| S-EPMC6431206 | biostudies-literature
| S-EPMC2516265 | biostudies-literature
| S-EPMC1890485 | biostudies-literature
| S-EPMC3177063 | biostudies-literature
| S-EPMC9057637 | biostudies-literature
2013-12-11 | E-GEOD-49018 | biostudies-arrayexpress
| S-EPMC5950008 | biostudies-literature
2013-12-11 | E-GEOD-49017 | biostudies-arrayexpress
2013-12-11 | GSE49018 | GEO