GA-guided mD-VcMD: A genetic-algorithm-guided method for multi-dimensional virtual-system coupled molecular dynamics

Biophysics and Physicobiology

Yoshifumi Fukunishi¹  Takuya Takahashi²  Kota Kasahara²  Xie Qilin³  Itaya Hayato⁴  Narutoshi Kamiya⁵  Junichi Higo⁵  Ikuo Fukuda⁵  Kentaro Mori⁵  Yutaka Hata⁵  Ayumi Kusaka⁶ 

[1] Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo, 135-0064, Japan;College of Life Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan;College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan;Graduate School of Life Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan;Graduate School of Simulation Studies, University of Hyogo, Kobe, Hyogo 650-0047, Japan;Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan;

关键词: canonical ensemble;    computer simulation;    conformational sampling;    enhanced sampling;    generalized ensemble;   

DOI  :  10.2142/biophysico.BSJ-2020008

来源: DOAJ

【 摘 要 】

We introduced a conformational sampling method in an earlier report: The multi-dimensional virtual-system coupled molecular dynamics (mD-VcMD) enhances conformational sampling of a biomolecular system by computer simulations. Herein, new sampling method, a subzone-based mD-VcMD, is presented as an extension of mD-VcMD. Then, the subzone-based method is extended further using a genetic algorithm (GA) named the GA-guided mD-VcMD. In these methods, iterative simulation runs are performed to increase the sampled region gradually. The new methods have the following benefits: (1) They are free from a production run: i.e., all snapshots from all iterations are useful for analyses. (2) They are free from fine tuning of a weight function (probability distribution function or potential of mean force). (3) A canonical ensemble (i.e., a thermally equilibrated ensemble) is generated from a simple procedure. A thermodynamic weight is assigned to each snapshot. (4) Selective sampling can be performed for particularly addressing a poorly sampled region without breaking the proportion of the canonical ensemble if the poorly sampled conformational region emerges in sampling. By applying the methods to a simple system that involves an energy barrier between potential-energy minima, we demonstrated that the new methods have considerably higher sampling efficiency than the original mD-VcMD does.

【 授权许可】

Unknown