biostudies-literatureAl-Subaie AMImam Abdulrahman Bin Faisal University7602https://www.ebi.ac.uk/biostudies/studies/S-EPMC8303888biostudies-literatureUnknown22(14)FMS-like tyrosine kinase 3 (FLT3) gene mutations have been found in more than one-third of Acute Myeloid Leukemia (AML) cases. The most common point mutation in FLT3 occurs at the 835th residue (D835A/E/F/G/H/I/N/V/Y), in the activation loop region. The D835 residue is critical in maintaining FLT3 inactive conformation; these mutations might influence the interaction with clinically approved AML inhibitors used to treat the AML. The molecular mechanism of each of these mutations and their interactions with AML inhibitors at the atomic level is still unknown. In this manuscript, we have investigated the structural consequence of native and mutant FLT-3 proteins and their molecular mechanisms at the atomic level, using molecular dynamics simulations (MDS). In addition, we use the molecular dInternational journal of molecular sciencesThe Structural Effect of FLT3 Mutations at 835th Position and Their Interaction with Acute Myeloid Leukemia Inhibitors: In Silico Approach.PMC8303888This work was primarily supported by grants from the newly recruited faculty program, Deanship of Scientific Research, Imam Abdulrahman Bin Faisal University (Grant No. 2019-162-AMSJ), Dammam, Saudi Arabia.Al-Subaie AMKamaraj BfalseThe Structural Effect of FLT3 Mutations at 835th Position and Their Interaction with Acute Myeloid Leukemia Inhibitors: In Silico Approach.FMS-like tyrosine kinase 3 (FLT3) gene mutations have been found in more than one-third of Acute Myeloid Leukemia (AML) cases. The most common point mutation in FLT3 occurs at the 835th residue (D835A/E/F/G/H/I/N/V/Y), in the activation loop region. The D835 residue is critical in maintaining FLT3 inactive conformation; these mutations might influence the interaction with clinically approved AML inhibitors used to treat the AML. The molecular mechanism of each of these mutations and their interactions with AML inhibitors at the atomic level is still unknown. In this manuscript, we have investigated the structural consequence of native and mutant FLT-3 proteins and their molecular mechanisms at the atomic level, using molecular dynamics simulations (MDS). In addition, we use the molecular d2021-01-01T00:00:00Z2021 Jul2026-04-08T06:55:47.004Z2022-02-11T00:12:05.689ZS-EPMC83038883429922210.3390/ijms22147602