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Evaluation of the absolute affinity of neuraminidase inhibitor using steered molecular dynamics simulations
Affiliation:1. Computational Chemistry Research Group, Ton Duc Thang University, Ho Chi Minh City, Vietnam;2. Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam;3. Institute for Computational Science and Technology (ICST), Quang Trung Software City, Ho Chi Minh City, Vietnam;4. Department of Chemistry, KU Leuven Celestijnenlaan 200F, B-3001 Leuven, Belgium;1. Institute of Fundamental Sciences, Massey University, Private Bag 11-222, Palmerston North, New Zealand;2. Riddet Institute, Massey University, Private Bag 11-222, Palmerston North, New Zealand;1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China;2. Institute of Poultry Science, Shandong Academy of Agricultural Sciences, 1, Jiaoxiao Road, Jinan, Shandong, 250023, PR China;3. College of Veterinary Medicine, South China Agricultural University, 483, Wushan Road, Tianhe District, Guangzhou, 510642, PR China;1. Applied Science College, Harbin University of Science and Technology, Harbin 150080, China;2. School of Materials Science and Engineering, Harbin University of Science and Technology, Harbin 150040, China;3. Department of the Applied Chemistry, Harbin Institute of Technology, Harbin 150001, China;1. Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio;2. The Ohio State Biochemistry Program, The Ohio State University, Columbus, Ohio;3. Biophysics Graduate Program, The Ohio State University, Columbus, Ohio;4. Chemical Physics Graduate Program, The Ohio State University, Columbus, Ohio;5. Facultad de Ingenieria y Tecnologia, Universidad San Sebastian, Santiago, Chile;1. Department of Biomedical Engineering;2. Department of Chemical Engineering;3. Department of Computer Science;4. University of California, Davis, Davis, California, Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL
Abstract:The absolute free energy difference of binding (ΔG) between neuraminidase and its inhibitor was evaluated using fast pulling of ligand (FPL) method over steered molecular dynamics (SMD) simulations. The metric was computed through linear interaction approximation. Binding nature was described by free energy differences of electrostatic and van der Waals (vdW) interactions. The finding indicates that vdW metric is dominant over electrostatics in binding process. The computed values are in good agreement with experimental data with a correlation coefficient of R = 0.82 and error of σΔGexp = 2.2 kcal/mol. The results were observed using Amber99SB-ILDN force field in comparison with CHARMM27 and GROMOS96 43a1 force fields. Obtained results may stimulate the search for an Influenza therapy.
Keywords:Fast pulling of ligand  Neuraminidase  NEMD  Absolute affinity  Interaction energy  Pulling work
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