Extended phase-space methods for enhanced sampling in molecular simulations: a review

Frontiers in Bioengineering and Biotechnology

Luca eMaragliano¹  Tetsuya eMorishita²  Hiroshi eFujisaki³  Yasuhiro eMatsunaga⁴  Kei eMoritsugu⁵ 

[1] Italian Institute of Technology;National Institute of Advanced Industrial Science and Technology (AIST);Nippon Medical School;Riken;Yokohama City University;

关键词: free energy;    molecular dynamics;    conformational transitions;    Rare events;    Protein-ligand binding;    Biomolecular interactions;   

DOI  :  10.3389/fbioe.2015.00125

来源: DOAJ

【 摘 要 】

Molecular Dynamics simulations are a powerful approach to study biomolecular conformational changes or protein-ligand, protein-protein and protein-DNA/RNA interactions. Straightforward applications however are often hampered by incomplete sampling, since in a typical simulated trajectory the system will spend most of its time trapped by high energy barriers in restricted regions of the configuration space. Over the years, several techniques have been designed to overcome this problem and enhance space sampling. Here, we review a class of methods that rely on the idea of extending the set of dynamical variables of the system by adding extra ones associated to functions describing the process under study. In particular, we illustrate the Temperature Accelerated Molecular Dynamics (TAMD), Logarithmic Mean Force Dynamics (LogMFD), andMultiscale Enhanced Sampling (MSES) algorithms. We also discuss combinations with techniques for searching reaction paths. We show the advantagespresented by this approach and how it allows to quickly sample important regions of the free energy landscape via automatic exploration.

【 授权许可】

Unknown