Daniel M. Zuckerman
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View article: Design of facilitated dissociation enables timing of cytokine signalling
Design of facilitated dissociation enables timing of cytokine signalling Open
View article: Combining datasets for Bayesian inference
Combining datasets for Bayesian inference Open
Bayesian inference (BI) has long been used to estimate posterior parameter distributions based on multiple sets of data. Here, we present elementary derivations of two strategies for doing so. The first approach employs the posterior distr…
View article: Improving parameter inference by resolving Bayesian prior ambiguity via multi-dataset analysis: Application to isothermal titration calorimetry
Improving parameter inference by resolving Bayesian prior ambiguity via multi-dataset analysis: Application to isothermal titration calorimetry Open
Isothermal titration calorimetry (ITC) is a powerful technique for probing biomolecular interactions. However, accurate determination of binding parameters—such as enthalpy and free energy—as well as associated uncertainties can be hindere…
View article: Molecular dynamics (Chapter 3)
Molecular dynamics (Chapter 3) Open
This chapter introduces molecular dynamics (MD), both as a principle of nature and as a computational method. A simple numerical recipe for classical MD is provided, along with key ingredients of common force fields which govern MD simulat…
View article: Weighted Ensemble Simulation: Advances in methods, software, and applications
Weighted Ensemble Simulation: Advances in methods, software, and applications Open
For more than two decades, weighted ensemble (WE) path sampling strategies have enabled the simulation of pathways for rare events—or barrier-crossing processes—with significantly less computing cost than conventional simulations, all whil…
View article: Inferring single-cell dynamics of a molecular reporter from unlabeled live-cell light microscopy data analyzed with delay embedding
Inferring single-cell dynamics of a molecular reporter from unlabeled live-cell light microscopy data analyzed with delay embedding Open
Quantification of the temporal sequence of molecular behavior in live individual cells holds promise for improving causal and mechanistic models of cell biology. In recent years, different methods for inferring molecular labeling from micr…
View article: Design of facilitated dissociation enables control over cytokine signaling duration
Design of facilitated dissociation enables control over cytokine signaling duration Open
Protein design has focused primarily on the design of ground states, ensuring they are sufficiently low energy to be highly populated. Designing the kinetics and dynamics of a system requires, in addition, the design of excited states that…
View article: Bayesian Mechanistic Inference, Statistical Mechanics, and a New Era for Monte Carlo
Bayesian Mechanistic Inference, Statistical Mechanics, and a New Era for Monte Carlo Open
On the one hand, much of computational chemistry is concerned with "bottom-up" calculations which elucidate observable behavior starting from exact or approximated physical laws, a paradigm exemplified by typical quantum mechanical calcula…
View article: Cycles, cooperativity, and molecular machines (Chapter 8)
Cycles, cooperativity, and molecular machines (Chapter 8) Open
Molecular machines such as transporters, motors, and genome processors underpin much of cell biology, and these in turn must be understood using biochemical cycles. This chapter lays out the basic biophysics of cycles, from rate constants …
View article: Single-cell morphodynamical trajectories enable prediction of gene expression accompanying cell state change
Single-cell morphodynamical trajectories enable prediction of gene expression accompanying cell state change Open
Extracellular signals induce changes to molecular programs that modulate multiple cellular phenotypes, including proliferation, motility, and differentiation status. The connection between dynamically adapting phenotypic states and the mol…
View article: RiteWeight: Randomized Iterative Trajectory Reweighting for Steady-State Distributions Without Discretization Error
RiteWeight: Randomized Iterative Trajectory Reweighting for Steady-State Distributions Without Discretization Error Open
A significant challenge in molecular dynamics (MD) simulations is ensuring that sampled configurations converge to the equilibrium or nonequilibrium stationary distribution of interest. Lack of convergence constrains the estimation of free…
View article: Bayesian mechanistic inference, statistical mechanics, and a new era for Monte Carlo
Bayesian mechanistic inference, statistical mechanics, and a new era for Monte Carlo Open
Much of computational chemistry is concerned with ``bottom-up'' calculations which elucidate observable behavior starting from exact or approximated physical laws, a paradigm exemplified by typical quantum mechanical calculations and molec…
View article: Combining datasets for Bayesian inference
Combining datasets for Bayesian inference Open
Bayesian inference (BI) has long been used to estimate posterior parameter distributions based on multiple sets of data. Here, we present elementary derivations of two strategies for doing so. The first approach employs the posterior distr…
View article: From average transient transporter currents to microscopic mechanism – A Bayesian analysis
From average transient transporter currents to microscopic mechanism – A Bayesian analysis Open
Electrophysiology studies of secondary active transporters have revealed quantitative, mechanistic insights over many decades of research. However, the emergence of new experimental and analysis approaches calls for investigation of the ca…
View article: Equilibrium statistical mechanics in two dimensions and beyond (Chapter 7)
Equilibrium statistical mechanics in two dimensions and beyond (Chapter 7) Open
This chapter introduces multi-dimensional statistical mechanics using the simplest square-well examples. From these, the concepts of free energy and entropy are quantified, highlighting similarities and differences from one dimension. Proj…
View article: Equilibrium statistical mechanics in one dimension (Chapter 6)
Equilibrium statistical mechanics in one dimension (Chapter 6) Open
This chapter introduces equilibrium statistical mechanics in one dimension based on the Boltzmann factor distribution. The concepts of free energy and entropy are quantified based on simple calculations of state populations. The harmonic a…
View article: Morphodynamical cell state description via live-cell imaging trajectory embedding
Morphodynamical cell state description via live-cell imaging trajectory embedding Open
Time-lapse imaging is a powerful approach to gain insight into the dynamic responses of cells, but the quantitative analysis of morphological changes over time remains challenging. Here, we exploit the concept of “trajectory embedding” to …
View article: Quantifying cooperative multisite binding in the hub protein LC8 through Bayesian inference
Quantifying cooperative multisite binding in the hub protein LC8 through Bayesian inference Open
Multistep protein-protein interactions underlie most biological processes, but their characterization through methods such as isothermal titration calorimetry (ITC) is largely confined to simple models that provide little information on th…
View article: Molecular dynamics (Chapter 3)
Molecular dynamics (Chapter 3) Open
This chapter introduces molecular dynamics (MD), both as a principle of nature and as a computational method. A simple numerical recipe for classical MD is provided, along with key ingredients of common force fields which govern MD simulat…
View article: From trajectories to conformational ensembles (Chapter 5)
From trajectories to conformational ensembles (Chapter 5) Open
This chapter presents a systematic analysis of trajectory ensembles in terms of conformational histograms (distributions) observed at different times. The basic mathematics of continuous probability distributions is introduced. One-dimensi…
View article: The trajectory ensemble (Chapter 4)
The trajectory ensemble (Chapter 4) Open
This chapter introduces the trajectory ensemble as the most fundamental description of nature, applicable to any system, whether in equilibrium or not. The trajectory ensembles considered in the chapter are collections of trajectories, e.g…
View article: ATP and the nonequilibrium wonderland of biology (Chapter 1)
ATP and the nonequilibrium wonderland of biology (Chapter 1) Open
This chapter introduces key principles of nonequilibrium science. Nonequilibrium phenomena are everywhere around us, and inside us, because any system that takes in (or gives off) energy or matter is out of equilibrium. The chapter focuses…
View article: Nonequilibrium physics in two and three states (Chapter 2)
Nonequilibrium physics in two and three states (Chapter 2) Open
This chapter uses the simplest systems, with two or three discrete states, to study core elements of nonequilibrium science. Two-state biochemical models include (idealized) protein folding and conformational switches. Using the standard d…
View article: Investigating LC8 Cooperativity via Molecular Dynamics
Investigating LC8 Cooperativity via Molecular Dynamics Open
The hub protein LC8, interacts with over 100 binding partners in the cell and participates in a range of cell activities including mitosis and viral interactions. LC8 is a symmetric homodimer with two identical binding grooves that typical…
View article: Morphodynamical cell-state description via live-cell imaging trajectory embedding
Morphodynamical cell-state description via live-cell imaging trajectory embedding Open
Time-lapse imaging is a powerful approach to gain insight into the dynamic responses of cells, but the quantitative analysis of morphological changes over time is a challenge. Here, we exploit the concept of "trajectory embedding" to analy…
View article: Weighted ensemble: Recent mathematical developments
Weighted ensemble: Recent mathematical developments Open
Weighted ensemble (WE) is an enhanced sampling method based on periodically replicating and pruning trajectories generated in parallel. WE has grown increasingly popular for computational biochemistry problems due, in part, to improved har…
View article: Maximum Likelihood vs. Bayesian estimation of uncertainty
Maximum Likelihood vs. Bayesian estimation of uncertainty Open
When a physical or mathematical model is inferred from experimental data, it is essential to assess uncertainties in model parameters, if only because highly uncertain parameters effectively have not been learned from the data. This discus…
View article: A Suite of Advanced Tutorials for the WESTPA 2.0 Rare-Events Sampling Software [Article v0.1]
A Suite of Advanced Tutorials for the WESTPA 2.0 Rare-Events Sampling Software [Article v0.1] Open
We present six advanced tutorials instructing users in the best practices of using key new features and plugins/extensions of the WESTPA 2.0 software package, which consists of major upgrades for enabling applications of the weighted ensem…
View article: #COVIDisAirborne: AI-enabled multiscale computational microscopy of delta SARS-CoV-2 in a respiratory aerosol
#COVIDisAirborne: AI-enabled multiscale computational microscopy of delta SARS-CoV-2 in a respiratory aerosol Open
We seek to completely revise current models of airborne transmission of respiratory viruses by providing never-before-seen atomic-level views of the SARS-CoV-2 virus within a respiratory aerosol. Our work dramatically extends the capabilit…
View article: KATP MD Simulation Trajectories
KATP MD Simulation Trajectories Open
MD simulation trajectories of pancreatic KATP channel