biostudies-literatureUnknown19Hernandez-Alvarez LNSFFAPESPCoordenação de Aperfeiçoamento de Pessoal de Nível SuperiorDuring their life cycle, <i>Leishmania</i> parasites display a fine-tuned regulation of the mRNA translation through the differential expression of isoforms of eukaryotic translation initiation factor 4E (LeishIF4Es). The interaction between allosteric modulators such as 4E-interacting proteins (4E-IPs) and LeishIF4E affects the affinity of this initiation factor for the mRNA cap. Here, several computational approaches were employed to elucidate the molecular bases of the previously-reported allosteric modulation in <i>L. major</i> exerted by 4E-IP1 (Lm4E-IP1) on eukaryotic translation initiation factor 4E 1 (LmIF4E-1). Molecular dynamics (MD) simulations and accurate binding free energy calculations (Δ<i>G_bind</i> ) were combined with network-based modeling of residue-residue cComputational and structural biotechnology journal2027-2044https://www.ebi.ac.uk/biostudies/studies/S-EPMC8085901biostudies-literatureComputational study on the allosteric mechanism of <i>Leishmania major</i> IF4E-1 by 4E-interacting protein-1: Unravelling the determinants of m⁷GTP cap recognition.PMC8085901Hernandez-Alvarez LOliveira ABde Souza FPde Araujo ASHernandez-Gonzalez JEChahine JPascutti PGfalseComputational study on the allosteric mechanism of <i>Leishmania major</i> IF4E-1 by 4E-interacting protein-1: Unravelling the determinants of m⁷GTP cap recognition.During their life cycle, <i>Leishmania</i> parasites display a fine-tuned regulation of the mRNA translation through the differential expression of isoforms of eukaryotic translation initiation factor 4E (LeishIF4Es). The interaction between allosteric modulators such as 4E-interacting proteins (4E-IPs) and LeishIF4E affects the affinity of this initiation factor for the mRNA cap. Here, several computational approaches were employed to elucidate the molecular bases of the previously-reported allosteric modulation in <i>L. major</i> exerted by 4E-IP1 (Lm4E-IP1) on eukaryotic translation initiation factor 4E 1 (LmIF4E-1). Molecular dynamics (MD) simulations and accurate binding free energy calculations (Δ<i>G_bind</i> ) were combined with network-based modeling of residue-residue c2021-01-01T00:00:00Z20212026-05-10T03:27:40.018Z2022-02-10T10:49:35.847ZS-EPMC80859013399590010.1016/j.csbj.2021.03.036