Viviane Garcia da Silva Alves, Maria Carliana Mota, Carla Pagliari
SOCIODEMOGRAPHIC CHARACTERISTICS RELATED TO KNOWING THE BENEFITS OF BREASTFEEDING
Revista paulista de pediatria : orgao oficial da Sociedade de Pediatria de Sao Paulo
understanding mechanisms allosteric regulation remains elusive sarscov2 spike protein despite increasing interest effort discovering allosteric inhibitors viral activity interactions host receptor ace2 challenges discovering allosteric modulators sarscov2 spike proteins associated diversity cryptic allosteric sites complex molecular mechanisms employed allosteric ligands including alteration conformational equilibrium spike protein preferential stabilization specific functional states current study combine conformational dynamics analysis distinct forms fulllength spike protein trimers machinelearningbased binding pocket detection ensemblebased ligand docking binding free energy analysis characterize potential allosteric binding sites determine structural energetic determinants allosteric inhibition series experimentally validated allosteric molecules results demonstrate good agreement computational experimental binding affinities providing support predicted binding modes suggesting key interactions formed allosteric ligands elicit experimentally observed inhibition establish structural energetic determinants allosteric binding experimentally known allosteric molecules indicating potential mechanism allosteric modulation targeting hinges interprotomer movements blocking conformational changes closed open spike trimer forms results study demonstrate combining ensemblebased ligand docking conformational states spike protein rigorous binding energy analysis enables robust characterization ligand binding modes identification allosteric binding hotspots prediction binding affinities validated allosteric modulators consistent experimental data study suggested conformational adaptability protein allosteric sites diversity ligand bound conformations play enable efficient targeting allosteric binding sites interfere conformational changes