A molecular simulation protocol to avoid sampling redundancy and discover new states

摘要: Abstract Background For biomacromolecules or their assemblies, experimental knowledge is often restricted to specific states. Ambiguity pervades simulations of these complex systems because there no prior relevant phase space domains, and sampling recurrence difficult achieve. In molecular dynamics methods, ruggedness the free energy surface exacerbates this problem by slowing down unbiased exploration space. Sampling inefficient if dwell times in metastable states are large. Methods We suggest a heuristic algorithm terminate reseed trajectories run multiple copies parallel. It uses recent method order snapshots, which provides notions “interesting” “unique” for individual simulations. define criteria guide reseeding runs from more points they sample overlapping regions Results Using pedagogical example an α-helical peptide, approach demonstrated amplify rate discover not found conventional schemes. Evidence provided that accurate kinetics pathways can be extracted Conclusions The method, termed PIGS Progress Index Guided Sampling, proceeds unsupervised fashion, scalable, benefits synergistically larger numbers replicas. confirm underlying ideas appropriate sufficient enhance sampling. General Significance simulations, errors caused exploring domains always unquantifiable arbitrarily Our protocol adds toolkit available researchers reducing types errors. This article part Special Issue entitled “Recent Developments Molecular Dynamics.”