Biomedical Engineering Reference
In-Depth Information
Advanced Molecular Modeling Techniques
Applied to Ion Channels Blockers
Supa Hannongbua, Witcha Treesuwan, and Warabhorn Boonyarat
Contents
1 Significance and Background ................................................................ 55
1.1 Ion Channels as Targets for Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
1.2 Type of Ion Channels . ................................................................. 56
1.3 Function of Ion Channels Blockers . .................................................. 57
1.4 Current Advanced Molecular Modeling Techniques Applied on Ion Channels
Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
2 Molecular Docking of the Ion Channels Blockers .......................................... 58
2.1 Exploration of the Binding Sites on Ion Channels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
2.2 Exploration of the Bound Blocker Conformation .................................... 59
2.3 Discovery of Novel Blockers by Virtual Screening . ................................. 60
3 MD Simulations of Ion Channels Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
3.1 Homology Modeling of Ion Channel Models ......................................... 62
3.2 MD Simulations to Describe Ion Channel Blocking Mechanism .................... 63
3.3 MD Simulation Protocols .............................................................. 64
4 QSAR Study on Ion Channels Blockers .................................................... 65
4.1 Principle of QSAR Methodology . . . .................................................. 66
4.2 2D-QSAR of Ion Channels Blockers .................................................. 66
4.3 3D-QSAR of Ion Channels Blockers .................................................. 67
4.4 4D-QSAR of Ion Channels Blockers .................................................. 67
5 ADMET Prediction of Ion Channels Blockers .............................................. 68
6 Quantum Chemical Calculations of Ion Channels Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
6.1 Applications of Ab-Initio and DFT Methods . . . ...................................... 69
6.2 Applications of QM/MM Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
7 Outlook and Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Abstract Drug molecules which can block the function of ion channels are
important in the treatment of several disorders which are all generally characterized
by abnormal membrane excitability, that is autoimmune disorders, hypertension,
