A comprehensive ensemble model for comparing the allosteric effect of ordered and disordered proteins

Luhao Zhang; Maodong Li; Zhirong Liu

doi:10.1371/journal.pcbi.1006393

A comprehensive ensemble model for comparing the allosteric effect of ordered and disordered proteins

PLoS Comput Biol. 2018 Dec 3;14(12):e1006393. doi: 10.1371/journal.pcbi.1006393. eCollection 2018 Dec.

Authors

Luhao Zhang^{1

2}, Maodong Li³, Zhirong Liu^{1

3

4}

Affiliations

¹ College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
² Department of Chemistry, Princeton University, Princeton, NJ, United States of America.
³ Center for Quantitative Biology, Peking University, Beijing, China.
⁴ State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Beijing National Laboratory for Molecular Sciences (BNLMS), Peking University, Beijing, China.

Abstract

Intrinsically disordered proteins/regions (IDPs/IDRs) are prevalent in allosteric regulation. It was previously thought that intrinsic disorder is favorable for maximizing the allosteric coupling. Here, we propose a comprehensive ensemble model to compare the roles of both order-order transition and disorder-order transition in allosteric effect. It is revealed that the MWC pathway (order-order transition) has a higher probability than the EAM pathway (disorder-order transition) in allostery, suggesting a complicated role of IDPs/IDRs in regulatory proteins. In addition, an analytic formula for the maximal allosteric coupling response is obtained, which shows that too stable or too unstable state is unfavorable to endow allostery, and is thus helpful for rational design of allosteric drugs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Allosteric Regulation
Amino Acids / chemistry
Entropy
Intrinsically Disordered Proteins / metabolism*
Models, Molecular
Molecular Dynamics Simulation / statistics & numerical data*
Probability
Protein Conformation
Proteins / chemistry*
Thermodynamics

Substances

Amino Acids
Intrinsically Disordered Proteins
Proteins

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant 21633001) (URL: http://www.nsfc.gov.cn/english/site_1/index.html) and the Ministry of Science and Technology of China (grant 2015CB910300)(URL: http://www.most.gov.cn/eng/). ZL is the author that received the funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.