Timewarp: Transferable Acceleration of Molecular Dynamics by Learning Time-Coarsened Dynamics

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Abstract: Molecular dynamics (MD) simulation is a widely used technique to simulate molecular systems, most commonly at the all-atom resolution where the equations of motion are integrated with timesteps on the order of femtoseconds (1fs=10−15s). MD is often used to compute equilibrium properties, which requires sampling from an equilibrium distribution such as the Boltzmann distribution. However, many important processes, such as binding and folding, occur over timescales of milliseconds or beyond, and cannot be efficiently sampled with conventional MD. Furthermore, new MD simulations need to be performed from scratch for each molecular system studied. We present Timewarp, an enhanced sampling method which uses a normalising flow as a proposal distribution in a Markov chain Monte Carlo method targeting the Boltzmann distribution. The flow is trained offline on MD trajectories and learns to make large steps in time, simulating the molecular dynamics of 105−106fs. Crucially, Timewarp is transferable between molecular systems: once trained, we show that it generalises to unseen small peptides (2-4 amino acids), exploring their metastable states and providing wall-clock acceleration when sampling compared to standard MD. Our method constitutes an important step towards developing general, transferable algorithms for accelerating MD.

Speakers:

Andrew Y. K. Foong - https://portal.valencelabs.com/member...
Leon Klein - https://portal.valencelabs.com/member...

Twitter Hannes:   / hannesstaerk  
Twitter Dominique:   / dom_beaini  

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Chapters
00:00 - Intro
00:51 - Molecular dynamics
04:48 - Datasets
08:13 - Conditional noarmalizing flows
15:30 - Atom transformer and kernel self-attention
26:49 - Augmented MCMC
37:22 - Batching the timewarp MCMC algorithm
40:42 - Training trajectories
51:52 - Timewarp MCMC
1:02:01 - Validation of new metastable states
1:09:18 - Summary
1:10:05 - Q+A