Dissecting the
Energetics of Intrinsically Disordered
Proteins via a Hybrid Experimental and Computational Approach
Posted on 2019-12-02 - 23:29
Intrinsically disordered proteins (IDPs) play important
roles in
biology, but little is known about the energetics of their inter-residue
interactions. Methods that have been successfully applied to analyze
the energetics of globular proteins are not applicable to the fluctuating
partially ordered ensembles populated by IDPs. A combined computational
experimental strategy is introduced for analyzing the energetic role
of individual residues in the free state of IDPs. The approach combines
experimental measurements of the binding of wild-type and mutant IDPs
to their partners with alchemical free energy calculations of the
structured complexes. These data allow quantitative information to
be deduced about the free state via a thermodynamic cycle. The approach
is validated by the analysis of the effects of mutations upon the
binding free energy of the ovomucoid inhibitor third binding domain
to its partners and is applied to the C-terminal domain of the measles
virus nucleoprotein, a 125-residue IDP involved in the RNA transcription
and replication of measles virus. The analysis reveals significant
inter-residue interactions in the unbound IDP and suggests a biological
role for them. The work demonstrates that advances in force fields
and computational hardware have now led to the point where it is possible
to develop methods, which integrate experimental and computational
techniques to reveal insights that cannot be studied using either
technique alone.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Zou, Junjie; Simmerling, Carlos; Raleigh, Daniel P. (2019). Dissecting the
Energetics of Intrinsically Disordered
Proteins via a Hybrid Experimental and Computational Approach. ACS Publications. Collection. https://doi.org/10.1021/acs.jpcb.9b08323
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (3)
JZ
Junjie Zou
CS
Carlos Simmerling
DR
Daniel P. Raleigh