Applying ultra-accelerated quantum chemical molecular dynamics technique for the evaluation of ligand protein interactions

Kamlesh Kumar Sahu, Mohamed Ismael, Shah Md Abdur Rauf, Ai Suzuki, Riadh Sahnoun, Michihisa Koyama, Hideyuki Tsuboi, Nozomu Hatakeyama, Akira Endou, Hiromitsu Takaba, Ramesh Chandra Deka, Carlos A. Del Carpio, Momoji Kubo, Akira Miyamoto

    Research output: Contribution to journalArticlepeer-review

    4 Citations (Scopus)


    Ligand-protein interactions have been studied using several chemical information techniques including quantum chemical methods that are applied to truncated systems composed of the ligand molecule and the surrounding amino acids of the receptor. Fragmented quantum molecular chemical studies are also a choice to study the enzyme-ligand system holistically, however there are still restrictions on the number of water molecules that can be included in a study of this nature. In this work we adopt a completely different approach to study ligand-protein interactions accounting explicitly for as many solvent molecules as possible and without the need for a fragmented calculation. Furthermore, we embed our quantum chemical calculations within a molecular dynamics framework that enables a fundamentally fast system for quantum chemical molecular dynamic simulations (QCMD). Central to this new system for QCMD is the tight binding QC system, newly developed in our laboratories, which combined with the MD paradigm results in an ultra-accelerated QCMD method for protein-ligand interaction evaluations. We have applied our newly developed system to the dihydrofolate reductase (DHFR)-methotrexate (MTX) system. We show how the proposed method leads us to new insights into the main interactions that bind MTX to the enzyme, mainly the interaction between the amino group of MTX and Asp27 of DHFR, as well as MTX amino group with Thr113 of DHFR, which have been only elucidated experimentally to date.

    Original languageEnglish
    Pages (from-to)1-10
    Number of pages10
    JournalMedicinal Chemistry Research
    Issue number1
    Publication statusPublished - Feb 2010

    All Science Journal Classification (ASJC) codes

    • Pharmacology, Toxicology and Pharmaceutics(all)
    • Organic Chemistry


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