@article{bibcite_649,
  keywords = {SEED, molecular dynamics simulations, allostery, integrins},
  author = {I. M. Ilie and C. Ehrhardt and A. Caflisch and G. Weitz-Schmidt},
  title = {Decrypting Integrins by mixed-solvent molecular dynamics simulations},
  abstract = {<p>Integrins are a family of \&alpha;/\&beta; heterodimeric cell surface adhesion receptors which are capable of transmitting signals bidirectionally across membranes. They are known for their therapeutic potential in a wide range of diseases. However, the development of integrin-targeting medications has been impacted by unexpected downstream effects including unwanted agonist-like effects. Allosteric modulation of integrins is a promising approach to potentially overcome these limitations. Applying mixed-solvent molecular dynamics (MD) simulations to integrins, the current study uncovers hitherto unknown allosteric sites within the integrin \&alpha; I domains of LFA-1 (\&alpha;L\&beta;2; CD11a/CD18), VLA-1 (\&alpha;1\&beta;1; CD49a/CD29), and Mac-1 (\&alpha;M\&beta;2, CD11b/CD18). We show that these pockets are putatively accessible to small-molecule modulators. The findings reported here may provide opportunities for the design of novel allosteric integrin inhibitors lacking the unwanted agonism observed with earlier as well as current integrin-targeting drugs.</p>},
  year = {2023},
  journal = {Journal of Chemical Information and Modeling},
  volume = {63},
  pages = {3878{\textendash}3891},
  month = {2023 June 13},
  doi = {10.1021/acs.jcim.3c00480},
  language = {eng},
}