Mechanical Strength of 17 134 Model Proteins and Cysteine Slipknots

Mateusz Sikora,Joanna I Sułkowska,Marek Cieplak,Angel Garcia

doi:10.1371/journal.pcbi.1000547

Abstract

A new theoretical survey of proteins' resistance to constant speed stretching is performed for a set of 17 134 proteins as described by a structure-based model. The proteins selected have no gaps in their structure determination and consist of no more than 250 amino acids. Our previous studies have dealt with 7510 proteins of no more than 150 amino acids. The proteins are ranked according to the strength of the resistance. Most of the predicted top-strength proteins have not yet been studied experimentally. Architectures and folds which are likely to yield large forces are identified. New types of potent force clamps are discovered. They involve disulphide bridges and, in particular, cysteine slipknots. An effective energy parameter of the model is estimated by comparing the theoretical data on characteristic forces to the corresponding experimental values combined with an extrapolation of the theoretical data to the experimental pulling speeds. These studies provide guidance for future experiments on single molecule manipulation and should lead to selection of proteins for applications. A new class of proteins, involving cystein slipknots, is identified as one that is expected to lead to the strongest force clamps known. This class is characterized through molecular dynamics simulations.

Highlights

Atomic force microscopy, optical tweezers, and other tools of nanotechnology have enabled induction and monitoring of large conformational changes in biomolecules
The contact map is determined by assigning the van der Waals spheres to the heavy atoms and by checking whether spheres belonging to different amino acids overlap in the native state [15,16]
We identify the CATH-based architectures and SCOP-based folds that are associated with the occurrence of a strong resistance to pulling

Summary

Introduction

Atomic force microscopy, optical tweezers, and other tools of nanotechnology have enabled induction and monitoring of large conformational changes in biomolecules. The contact map is determined by assigning the van der Waals spheres to the heavy atoms (enlarged by a factor to account for attraction) and by checking whether spheres belonging to different amino acids overlap in the native state [15,16]. If they do, a contact is declared as native. Waals couplings as can be demonstrated in a sample of proteins by using a software [17] which analyses atomic configurations from the

Author Summary

Findings

Materials and Methods