Next Article in Journal
Synthesis and Evaluation of a Rationally Designed Click-Based Library for G-Quadruplex Selective DNA Photocleavage
Next Article in Special Issue
Comparative Analysis of Virtual Screening Approaches in the Search for Novel EphA2 Receptor Antagonists
Previous Article in Journal
Synthesis, Antibacterial and Antitubercular Activities of Some 5H-Thiazolo[3,2-a]pyrimidin-5-ones and Sulfonic Acid Derivatives
Article Menu

Export Article

Open AccessReview
Molecules 2015, 20(9), 16435-16445;

Small Molecule Targeting of Protein–Protein Interactions through Allosteric Modulation of Dynamics

Computer-Aided Drug Design and Structural Biology, UCB, 216 Bath Road, Slough, SL1 3WE, UK
Author to whom correspondence should be addressed.
Academic Editor: Philippe Roche
Received: 7 August 2015 / Revised: 6 September 2015 / Accepted: 8 September 2015 / Published: 10 September 2015
(This article belongs to the Special Issue Small Molecules Modulation in Protein-Protein Interactions)
Full-Text   |   PDF [667 KB, uploaded 10 September 2015]


The protein–protein interaction (PPI) target class is particularly challenging, but offers potential for “first in class” therapies. Most known PPI small molecules are orthosteric inhibitors but many PPI sites may be fundamentally intractable to this approach. One potential alternative is to consider more attractive, remote small molecule pockets; however, on the whole, allostery is poorly understood and difficult to discover and develop. Here we review the literature in order to understand the basis for allostery, especially as it can apply to PPIs. We suggest that the upfront generation of sophisticated and experimentally validated dynamic models of target proteins can aid in target choice and strategy for allosteric intervention to produce the required functional effect. View Full-Text
Keywords: protein–protein interaction; allosteric; protein dynamics; small molecule protein–protein interaction; allosteric; protein dynamics; small molecule
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Cossins, B.P.; Lawson, A.D.G. Small Molecule Targeting of Protein–Protein Interactions through Allosteric Modulation of Dynamics. Molecules 2015, 20, 16435-16445.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top