PMID- 35944496
OWN - NLM
STAT- MEDLINE
DCOM- 20221228
LR  - 20221228
IS  - 1520-5207 (Electronic)
IS  - 1520-5207 (Linking)
VI  - 126
IP  - 32
DP  - 2022 Aug 18
TI  - Salt-Induced Transitions in the Conformational Ensembles of Intrinsically 
      Disordered Proteins.
PG  - 5959-5971
LID - 10.1021/acs.jpcb.2c03476 [doi]
AB  - Salts modulate the behavior of intrinsically disordered proteins (IDPs) and 
      influence the formation of membraneless organelles through liquid-liquid phase 
      separation (LLPS). In low ionic strength solutions, IDP conformations are 
      perturbed by the screening of electrostatic interactions, independent of the salt 
      identity. In this regime, insight into the IDP behavior can be obtained using the 
      theory for salt-induced transitions in charged polymers. However, salt-specific 
      interactions with the charged and uncharged residues, known as the Hofmeister 
      effect, influence IDP behavior in high ionic strength solutions. There is a lack 
      of reliable theoretical models in high salt concentration regimes to predict the 
      salt effect on IDPs. We propose a simulation methodology using a coarse-grained 
      IDP model and experimentally measured water to salt solution transfer free 
      energies of various chemical groups that allowed us to study the salt-specific 
      transitions induced in the IDPs conformational ensemble. We probed the effect of 
      three different monovalent salts on five IDPs belonging to various polymer 
      classes based on charged residue content. We demonstrate that all of the IDPs of 
      different polymer classes behave as self-avoiding walks (SAWs) at physiological 
      salt concentration. In high salt concentrations, the transitions observed in the 
      IDP conformational ensembles are dependent on the salt used and the IDP sequence 
      and composition. Changing the anion with the cation fixed can result in the IDP 
      transition from a SAW-like behavior to a collapsed globule. An important 
      implication of these results is that a suitable salt can be identified to induce 
      condensation of an IDP through LLPS.
FAU - Maity, Hiranmay
AU  - Maity H
AD  - Solid State and Structural Chemistry Unit, Indian Institute of Science, 
      Bengaluru, Karnataka, India 560012.
FAU - Baidya, Lipika
AU  - Baidya L
AD  - Solid State and Structural Chemistry Unit, Indian Institute of Science, 
      Bengaluru, Karnataka, India 560012.
FAU - Reddy, Govardhan
AU  - Reddy G
AUID- ORCID: 0000-0002-9013-8040
AD  - Solid State and Structural Chemistry Unit, Indian Institute of Science, 
      Bengaluru, Karnataka, India 560012.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220809
PL  - United States
TA  - J Phys Chem B
JT  - The journal of physical chemistry. B
JID - 101157530
RN  - 0 (Intrinsically Disordered Proteins)
RN  - 0 (Polymers)
RN  - 0 (Salts)
RN  - 451W47IQ8X (Sodium Chloride)
SB  - IM
MH  - *Intrinsically Disordered Proteins/chemistry
MH  - Polymers
MH  - Protein Conformation
MH  - Salts
MH  - Sodium Chloride
EDAT- 2022/08/10 06:00
MHDA- 2022/08/20 06:00
CRDT- 2022/08/09 18:29
PHST- 2022/08/10 06:00 [pubmed]
PHST- 2022/08/20 06:00 [medline]
PHST- 2022/08/09 18:29 [entrez]
AID - 10.1021/acs.jpcb.2c03476 [doi]
PST - ppublish
SO  - J Phys Chem B. 2022 Aug 18;126(32):5959-5971. doi: 10.1021/acs.jpcb.2c03476. Epub 
      2022 Aug 9.