Molecular dynamics

Molecular dynamics

This page is a placeholder, or under current development; it is here principally to establish the logical framework of the site. The material on this page is correct, but incomplete.

Summary ...

 

Contents

   

Further reading and resources

Manibog et al. (2014) Resolving the molecular mechanism of cadherin catch bond formation. Nat Commun 5:3941. (pmid: 24887573)

[ PubMed ] [ DOI ] Abstract Classical cadherin Ca(2+)-dependent cell-cell adhesion proteins play key roles in embryogenesis and in maintaining tissue integrity. Cadherins mediate robust adhesion by binding in multiple conformations. One of these adhesive states, called an X-dimer, forms catch bonds that strengthen and become longer lived in the presence of mechanical force. Here we use single-molecule force-clamp spectroscopy with an atomic force microscope along with molecular dynamics and steered molecular dynamics simulations to resolve the molecular mechanisms underlying catch bond formation and the role of Ca(2+) ions in this process. Our data suggest that tensile force bends the cadherin extracellular region such that they form long-lived, force-induced hydrogen bonds that lock X-dimers into tighter contact. When Ca(2+) concentration is decreased, fewer de novo hydrogen bonds are formed and catch bond formation is eliminated.

Zhulin, IB (2013) on Anton

Ortega et al. (2013) A phenylalanine rotameric switch for signal-state control in bacterial chemoreceptors. Nat Commun 4:2881. (pmid: 24335957)

[ PubMed ] [ DOI ] Abstract Bacterial chemoreceptors are widely used as a model system for elucidating the molecular mechanisms of transmembrane signalling and have provided a detailed understanding of how ligand binding by the receptor modulates the activity of its associated kinase CheA. However, the mechanisms by which conformational signals move between signalling elements within a receptor dimer and how they control kinase activity remain unknown. Here, using long molecular dynamics simulations, we show that the kinase-activating cytoplasmic tip of the chemoreceptor fluctuates between two stable conformations in a signal-dependent manner. A highly conserved residue, Phe396, appears to serve as the conformational switch, because flipping of the stacked aromatic rings of an interacting F396-F396' pair in the receptor homodimer takes place concomitantly with the signal-related conformational changes. We suggest that interacting aromatic residues, which are common stabilizers of protein tertiary structure, might serve as rotameric molecular switches in other biological processes as well.