PLoS Comput Biol. 2016 Jun 23;12(6):e1004728. doi: 10.1371/journal.pcbi.1004728. eCollection 2016. Parton DL, Grinaway PB, Hanson SM, Beauchamp KA, Chodera JD. The rapidly expanding body of available genomic and protein…
Read moreThe rapidly expanding body of available genomic and protein structural data provides a rich resource for understanding protein dynamics with biomolecular simulation. While computational infrastructure has grown rapidly, simulations on an omics scale are not yet widespread, primarily because software infrastructure to enable simulations at this scale has not kept …
Read moreBiophys J. 2016 Apr 26;110(8):1716-9. doi: 10.1016/j.bpj.2016.03.026. Schwantes CR, Shukla D, Pande VS After reanalyzing simulations of NuG2-a designed mutant of protein G-generated by Lindorff-Larsen et al. with time structure-based independent…
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Nat Commun. 2016 Apr 4;7:10910. doi: 10.1038/ncomms10910. Shukla D ,Peck A , Pande VS Finally, our model predicts a novel binding interface that is well-populated in the Ca(2+)-bound regime and, thus, a…
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J Phys Chem B. 2016 Feb 11;120(5):926-35. doi: 10.1021/acs.jpcb.5b11767. Epub 2016 Feb 1. Zhou G, Voelz VA. Salt-bridge interactions play an important role in stabilizing many protein structures, and have…
Read morePeptoids (N-substituted oligoglycines) are biomimetic polymers that can fold into a variety of unique structural scaffolds. Peptoid helices, which result from the incorporation of bulky chiral side chains, are a key peptoid structural motif whose formation has not yet been accurately modeled in molecular simulations. Here, we report that a simple modification of the backbone φ-angle potential in GAFF is able to produce well-folded cis-amide helices of (S)-N-(1-phenylethyl)glycine (Nspe), consi…
Read moreMolecular dynamics simulations are a powerful means of understanding conformational changes. However, it is still difficult to simulate biologically relevant time scales without the use of specialized supercomputers. Here, we introduce a goal-oriented sampling method, called fluctuation amplification of specific traits (FAST), for extending the capabilities of commodity hardware. This algorithm rapidly searches conformational space for structures with desired properties by balancing trade-offs…
Read moreWe present an analysis of the most extensive explicit-solvent simulations of β-hairpins to date (9.4 ms in aggregate), with the aim of probing the effects of tryptophan mutations on folding. From molecular simulations of GB1 hairpin, trpzip4, trpzip5, and trpzip6 performed on Folding@home, Markov State Models (MSMs) were constructed using a unified set of metastable states, enabling objective comparison of folding mechanisms. MSM models display quantitative agreement with experimental structur…
Read moreMarkov state models (MSMs), which model conformational dynamics as a network of transitions between metastable states, have been increasingly used to model the thermodynamics and kinetics of biomolecules. In considering perturbations to molecular dynamics induced by sequence mutations, chemical modifications, or changes in external conditions, it is important to assess how transition rates change, independent of changes in metastable state definitions. Here, we present a surprisal metric to qu…
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