PMID- 37122440
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240303
IS  - 2513-0390 (Electronic)
IS  - 2513-0390 (Linking)
VI  - 6
IP  - 2
DP  - 2023 Feb
TI  - Rational Design of de novo CCL2 Binding Peptides.
LID - 2200810 [pii]
LID - 10.1002/adts.202200810 [doi]
AB  - Chronic levels of inflammation lead to autoimmune diseases such as rheumatoid 
      arthritis and atherosclerosis. A key molecular mediator responsible for the 
      progression of these diseases is Chemokine C-C motif ligand 2 (CCL2), a 
      homodimerized cytokine that dissociates into monomeric form and binds to the CCR2 
      receptor. CCL2, also known as monocyte chemoattractant protein-1 (MCP-1), 
      attracts monocytes to migrate to areas of injury and mature into macrophages, 
      leading to positive feedback inflammation with further release of proinflammatory 
      molecules such as IL-1beta and TNF-alpha. Sequestering CCL2 to prevent its binding to 
      CCR2 may prevent this inflammatory activity. Prior work adapted an alpha-helical 
      CCL2-binding peptide (WKNFQTI) from murine CCR2 through extracellular loop 
      analysis. Here, higher-affinity peptide binders were computationally designed 
      through homology modeling and energy calculations, yielding an 11-amino acid 
      peptide with high binding affinity. In addition, Rosetta mutations improved 
      binding affinity in silico with blockage of the CCL2 dimerization site. Future 
      work in analyzing binding kinetics and in vivo inflammation abrogation will 
      confirm the accuracy of computational modeling techniques in de novo rational 
      design of CCL2 cytokine binders.
FAU - Davidoff Aguas, Erika
AU  - Davidoff Aguas E
AD  - Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, 08544.
FAU - Azizogli, Abdul-Rahman
AU  - Azizogli AR
AD  - Department of Biological Sciences, New Jersey Institute of Technology, Newark, 
      NJ, 07102.
FAU - Kashyap, Jatin
AU  - Kashyap J
AD  - Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, 
      NJ, 07102.
FAU - Dodd-O, Joseph
AU  - Dodd-O J
AD  - Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, 
      NJ, 07102.
FAU - Siddiqui, Zain
AU  - Siddiqui Z
AD  - Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, 
      NJ, 07102.
FAU - Sy, Jay
AU  - Sy J
AD  - Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, 08544.
FAU - Kumar, Vivek
AU  - Kumar V
AD  - Department of Biological Sciences, New Jersey Institute of Technology, Newark, 
      NJ, 07102.
AD  - Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, 
      NJ, 07102.
AD  - Department of Chemical and Materials Engineering, New Jersey Institute of 
      Technology, Newark, NJ, 07102.
AD  - Department of Endodontics, Rutgers School of Dental Medicine, Newark, NJ, 07103.
LA  - eng
GR  - P41 RR012408/RR/NCRR NIH HHS/United States
GR  - R01 DE031812/DE/NIDCR NIH HHS/United States
GR  - T32 GM135141/GM/NIGMS NIH HHS/United States
GR  - R21 AR079708/AR/NIAMS NIH HHS/United States
GR  - R15 EY029504/EY/NEI NIH HHS/United States
PT  - Journal Article
DEP - 20221218
PL  - Germany
TA  - Adv Theory Simul
JT  - Advanced theory and simulations
JID - 101741467
PMC - PMC10139756
MID - NIHMS1859419
OTO - NOTNLM
OT  - CCR2
OT  - MCP-1
OT  - computational peptide design
OT  - inflammation
OT  - molecular docking
EDAT- 2023/05/01 06:42
MHDA- 2023/05/01 06:43
PMCR- 2023/04/27
CRDT- 2023/05/01 03:16
PHST- 2023/05/01 06:43 [medline]
PHST- 2023/05/01 06:42 [pubmed]
PHST- 2023/05/01 03:16 [entrez]
PHST- 2023/04/27 00:00 [pmc-release]
AID - 2200810 [pii]
AID - 10.1002/adts.202200810 [doi]
PST - ppublish
SO  - Adv Theory Simul. 2023 Feb;6(2):2200810. doi: 10.1002/adts.202200810. Epub 2022 
      Dec 18.