Pushing the boundaries of molecular dynamics simulations
소속 :
연사 : Prof. Ju yong Lee(강원대학교)
일시 : 2018-05-10 16:30 ~
장소 : 500동, 목암홀
In this talk, I will present advances in computational methods to bridge the gap
between computational and experimental methods to study the mechanisms of biomolecules. A brief introduction of the current stages of molecular dynamics and free energy calculations will be given. Afterwards, recent advances on molecular dynamics to overcome the limitations of current simulations will be presented based on three topics. First, I will present a new computational approach, Action-CSA, to find multiple reaction pathways with fixed initial and final states through global optimization of the Onsager-Machlup action using the conformational space annealing method1. This approach successfully finds all possible pathways of small systems without initial guesses on pathways. Pathway space is efficiently searched by crossover and mutation operations of a set of pathways and preserving the diversity of the set. The search efficiency of the approach is assessed by finding pathways for the conformational changes of alanine dipeptide and hexane. The benchmarks demonstrate that the rank order and the transition time distribution of multiple pathways identified by the new approach are in good agreement with those of long Langevin dynamics simulations. We also show that the lowest action folding pathways of the mini-protein FSD-1 identified by the new approach is consistent with previous molecular dynamics simulations and experiments. Second, I will present constant-pH molecular dynamics methods, which simulate spontaneous changes of protonation states of titratable residues2–4. The new methods yield the canonical ensemble of multiple protonation states. I will show how these methods are used to perform constant-pH free energy calculations. Third, a new hybrid protein model based on the combination of the physics-based model and the Go-model will be presented5. This method effectively samples the large-scale conformational changes of adenylate kinase between its open and closed states. The simulation results are showing a good agreement with the backbone fluctuation data obtained with NMR experiments. In summary, these methods will extend the timescale and chemical accuracy of molecular dynamics and free energy calculation methods, which will help to interpret experimental data using theoretical methods.
between computational and experimental methods to study the mechanisms of biomolecules. A brief introduction of the current stages of molecular dynamics and free energy calculations will be given. Afterwards, recent advances on molecular dynamics to overcome the limitations of current simulations will be presented based on three topics. First, I will present a new computational approach, Action-CSA, to find multiple reaction pathways with fixed initial and final states through global optimization of the Onsager-Machlup action using the conformational space annealing method1. This approach successfully finds all possible pathways of small systems without initial guesses on pathways. Pathway space is efficiently searched by crossover and mutation operations of a set of pathways and preserving the diversity of the set. The search efficiency of the approach is assessed by finding pathways for the conformational changes of alanine dipeptide and hexane. The benchmarks demonstrate that the rank order and the transition time distribution of multiple pathways identified by the new approach are in good agreement with those of long Langevin dynamics simulations. We also show that the lowest action folding pathways of the mini-protein FSD-1 identified by the new approach is consistent with previous molecular dynamics simulations and experiments. Second, I will present constant-pH molecular dynamics methods, which simulate spontaneous changes of protonation states of titratable residues2–4. The new methods yield the canonical ensemble of multiple protonation states. I will show how these methods are used to perform constant-pH free energy calculations. Third, a new hybrid protein model based on the combination of the physics-based model and the Go-model will be presented5. This method effectively samples the large-scale conformational changes of adenylate kinase between its open and closed states. The simulation results are showing a good agreement with the backbone fluctuation data obtained with NMR experiments. In summary, these methods will extend the timescale and chemical accuracy of molecular dynamics and free energy calculation methods, which will help to interpret experimental data using theoretical methods.
