PMID- 34105559
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20210616
LR  - 20210616
IS  - 1463-9084 (Electronic)
IS  - 1463-9076 (Linking)
VI  - 23
IP  - 23
DP  - 2021 Jun 16
TI  - Infrequent metadynamics study of rare-event electrostatic channeling.
PG  - 13381-13388
LID - 10.1039/d1cp01304a [doi]
AB  - The efficiency of cascade reactions, which consist of multiple chemical 
      transformations that occur in a single pot without purification steps, is limited 
      by the transport efficiency of intermediates between adjacent steps. 
      Electrostatic channeling is a proven strategy for intermediate transfer in 
      natural chemical cascades, but implementation into artificial cascades remains a 
      challenge. Here, we combine infrequent metadynamics (InMetaD), umbrella sampling 
      (US), and kinetic Monte Carlo (KMC) models to computationally study the transfer 
      mechanism of glucose-6-phosphate (G6P) on a poly-arginine peptide bridging 
      hexokinase (HK) and glucose-6-dehydrogenase (G6PDH). Transport of G6P by hopping 
      in the presence of poly-arginine peptides is shown to be a rare event, and 
      InMetaD is used to compute the hopping activation energy. US simulations capture 
      the configurational change in the desorption process and enable the determination 
      of the desorption energy. Parameterized by these results, a KMC model is used to 
      estimate transport efficiency for the bridged enzyme complex. Results are 
      compared to a similar complex using a poly-lysine bridge, using kinetic lag time 
      as a metric. Even at a high ionic strength of 120 mM, poly-arginine peptides may 
      be capable of more efficient transport as compared to poly-lysine, with a 
      predicted lag time of 6 seconds for poly-arginine, compared to a previously 
      reported lag time of 59 seconds for poly-lysine. This work indicates that 
      poly-arginine peptides may be an improved bridge structure for electrostatic 
      channeling of anionic intermediates.
FAU - Xie, Yan
AU  - Xie Y
AUID- ORCID: 0000-0002-3092-1033
AD  - Department of Chemical Engineering and Materials Science, Michigan State 
      University, East Lansing, MI 48824, USA. scb@msu.edu.
FAU - Calabrese Barton, Scott
AU  - Calabrese Barton S
AUID- ORCID: 0000-0002-1407-0275
AD  - Department of Chemical Engineering and Materials Science, Michigan State 
      University, East Lansing, MI 48824, USA. scb@msu.edu.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Phys Chem Chem Phys
JT  - Physical chemistry chemical physics : PCCP
JID - 100888160
SB  - IM
EDAT- 2021/06/10 06:00
MHDA- 2021/06/10 06:01
CRDT- 2021/06/09 08:48
PHST- 2021/06/10 06:00 [pubmed]
PHST- 2021/06/10 06:01 [medline]
PHST- 2021/06/09 08:48 [entrez]
AID - 10.1039/d1cp01304a [doi]
PST - ppublish
SO  - Phys Chem Chem Phys. 2021 Jun 16;23(23):13381-13388. doi: 10.1039/d1cp01304a.