Novel fluorescent antifolates that target folate receptors alpha and beta: Molecular dynamics and density functional theory study

摘要

Nine novel fluorescent antifolates, 1-9, were designed and docked with FR alpha and FR beta. The binding energies of the bound complexes were determined by molecular docking and MM-PBSA studies. The structural properties of the complexes FR-FOL, FR-7, FR-8 and FR-9 were analyzed in detail via molecular docking and molecular dynamics studies. We further calculated the root mean square displacement and root mean square fluctuation of the bound complexes using molecular dynamics simulations. Since compounds 7, 8 and 9 are promising candidate in distinguishing FR alpha from FR beta, the hydrogen bond properties of complexes FR alpha-7, FR alpha-8 and FR alpha-9 were studied by a dispersion complemented density functional tight-binding method. The purpose of this study is to provide a rationale for the design of novel fluorescent antifolates targeted with FR alpha and FR beta. (C) 2018 Elsevier Inc. All rights reserved.