High performance computing for drug development on K computer

24th IUPAP Conference on Computational Physics

物理学;计算机科学

Fujitani, Hideaki^1 ; Shinoda, Keiko^1 ; Yamashita, Takefumi^1 ; Kodama, Tatsuhiko^1

Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan^1

关键词: Ab initio molecular orbital theory;    Bennett acceptance ratio;    Binding free energy;    Computer aided drug design;    Force field parameters;    Free-energy difference;    High performance computing;    Massively parallels;   

Others  :  https://iopscience.iop.org/article/10.1088/1742-6596/454/1/012018/pdf
DOI  :  10.1088/1742-6596/454/1/012018

学科分类：计算机科学（综合）

来源: IOP

【 摘 要 】

Massively parallel computations (MP-CAFEE) ware developed to calculate absolute binding free energies of small molecules bound to a protein by all-atom molecular dynamics. It uses the nonequilibrium work measurement and Bennett acceptance ratio methods to calculate the free energy difference between the bound and unbound states. The FUJI force field was developed in order to assign force field parameters to arbitrary organic molecules in a unified manner including proteins and nucleic acids. Its dihedral parameters agree with the torsion energy profiles calculated by high-level ab initio molecular orbital theory for the model systems of protein backbone. Comparing with various force fields it agrees well with recent observations by vibrational spectroscopy on Ramachandran angle's population of alanine dipeptide in water. MP-CAFEE with FUJI force field has an efficient parallel algorithm and enough accuracy for computer aided drug design.