Mechanical Strength of 17 134 Model Proteins and Cysteine Slipknots

TL;DR

This study conducts a theoretical survey of 17,134 proteins to identify structures with high mechanical resistance, discovering new force clamps involving cysteine slipknots with potential applications in molecular manipulation.

Contribution

It introduces a large-scale structure-based model analysis of protein strength, identifying novel force clamps and the role of cysteine slipknots in mechanical resistance.

Findings

Most top-strength proteins are unstudied experimentally.

Discovered new force clamps involving disulphide bridges.

Identified cysteine slipknots as key to strong force resistance.

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.