PMID- 30379153
OWN - NLM
STAT- MEDLINE
DCOM- 20190708
LR  - 20190708
IS  - 1463-9084 (Electronic)
IS  - 1463-9076 (Linking)
VI  - 20
IP  - 44
DP  - 2018 Nov 14
TI  - Quantifying the protein-protein association rate in polymer solutions: 
      crowding-induced diffusion and energy modifications.
PG  - 27937-27948
LID - 10.1039/c8cp05203d [doi]
AB  - A theoretical framework is developed to study protein-protein association in 
      polymer solutions under diffusion-limited conditions. Starting from the basal 
      association rate, two fundamental aspects concerning macromolecular crowding are 
      particularly taken into account. One is the effect of microviscosity on protein 
      diffusion. The length-scale dependent relations of translational and rotational 
      diffusion coefficients are incorporated. Another is relevant to the 
      crowding-induced effective interaction between the pair of proteins. The 
      resultant energy modifications to the basal association rate are properly 
      introduced, following an instructive classification with increasing crowder size: 
      repulsive interaction dominant, repulsive and attractive interactions 
      competitive, and attractive interaction prevailing. With specific energy 
      modification terms, we are able to investigate the deviations of the association 
      rate from the Stokes-Einstein (SE) behavior (i.e., the linear relationship with 
      respect to the reciprocal of macroviscosity) in a quantitative manner. Our theory 
      is applied to study the association of TEM1-beta-lactamase (TEM) and the beta-lactamase 
      inhibitor protein (BLIP) in polyethylene glycol (PEG) solutions, with varying 
      concentration and polymerization. We explicitly evaluate the relative association 
      rate constant as a function of the solution macroviscosity. The theoretical 
      results demonstrate very good agreement with the experimental data. Moreover, the 
      complicated non-trivial deviations, either positive (slower than SE) or negative 
      (faster than SE), are systematically rationalized. The precise role of energy 
      modifications and the microviscosity effect on diffusion, in particular on 
      rotational diffusion, are clearly unraveled.
FAU - Qing, Jing
AU  - Qing J
AD  - College of Chemistry, Sichuan University, Chengdu 610064, China. 
      zhaonanr@scu.edu.cn.
FAU - Chen, Anpu
AU  - Chen A
FAU - Zhao, Nanrong
AU  - Zhao N
LA  - eng
PT  - Journal Article
PL  - England
TA  - Phys Chem Chem Phys
JT  - Physical chemistry chemical physics : PCCP
JID - 100888160
RN  - 0 (Solutions)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - EC 3.5.2.6 (beta-Lactamases)
SB  - IM
MH  - Binding Sites
MH  - Computer Simulation
MH  - Diffusion
MH  - Kinetics
MH  - *Models, Molecular
MH  - Physical Phenomena
MH  - Polyethylene Glycols/*chemistry
MH  - Polymerization
MH  - Protein Binding
MH  - Protein Conformation
MH  - Protein Multimerization
MH  - Solutions
MH  - Thermodynamics
MH  - Viscosity
MH  - beta-Lactamases/*chemistry
EDAT- 2018/11/01 06:00
MHDA- 2019/07/10 06:00
CRDT- 2018/11/01 06:00
PHST- 2018/11/01 06:00 [pubmed]
PHST- 2019/07/10 06:00 [medline]
PHST- 2018/11/01 06:00 [entrez]
AID - 10.1039/c8cp05203d [doi]
PST - ppublish
SO  - Phys Chem Chem Phys. 2018 Nov 14;20(44):27937-27948. doi: 10.1039/c8cp05203d.