Macromolecular Modeling, Nailing Allostery, and Drug-Centric Drug Development: the PLOS Comp Biol April Issue

Check out our highlights from the PLOS Computational Biology April Issue:

In this Review article, Amarda Shehu and colleagues provide an overview of recent advancements in computational methods for modeling macromolecular structure and dynamics. The focus is on methods aimed at providing efficient representations of macromolecular structure spaces for the purpose of characterizing equilibrium dynamics. The authors provide a summary of state-of-the-art capabilities of these methods from an application point of view, as well as highlighting important algorithmic contributions responsible for recent advances in macromolecular structure and dynamics modeling.
 

Rigid Residue Scan Simulations Systematically Reveal Residue Entropic Roles in Protein Allostery
Allostery is a fundamental dynamics property of many proteins, and plays a critical role in protein functions. Despite extensive studies of protein allosteric mechanisms, the current understanding and predicting power of protein allostery are still limited. One of the main challenges in studying protein allostery is effectively narrowing down residues for further site-directed mutagenesis study. Peng Tao and collagues significantly enhance a simulation method developed in their lab – rigid residue scan (RRS) – to systematically probe the impact of each individual residue on overall protein dynamics through rigid body molecular dynamics simulations using an efficient integrator.

A Drug-Centric View of Drug Development: How Drugs Spread from Disease to Disease

The number of drug-like chemical and biological substances that can be constructed with current technologies is vast, yet the subset that can become an effective drug is restricted due to design constraints and the expense of development. Once developed, however, a drug can have multiple biological effects that can be beneficial in a variety of diseases. Raul Rodriguez-Esteban shows that this combination of scarcity and polyvalence leads some drugs to propagate from disease to disease in a contagious manner. This analysis offers an alternative view of the drug development process in which drugs are central and can define dynamic relationships between diseases.

Header image credit: e-Magine Art/ Flickr