Some of my papers

Collection by Melanie Stefan

12 
Pins

Selected publications. For a full list, go to http://melaniestefan.net/publications.html

Melanie Stefan
M.I. Stefan (2010) A cv of failures Nature, 468, 467.m

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M.I. Stefan, T.M. Bartol, T.J. Sejnowski, M.B. Kennedy (2014) Multi-state Modeling of Biomolecules PLoS Comput Biol, 10(9): e1003844.

Multi-state Modeling of Biomolecules

Multi-state modeling of biomolecules refers to a series of techniques used to represent and compute the behavior of biological molecules or complexes that can adopt a large number of possible functional states. Biological signaling systems often rely on complexes of biological macromolecules that can undergo several functionally significant modifications that are mutually compatible. Thus, they can exist in a very large number of functionally different states. Modeling such multi-state…

MI Stefan, JL Gutlerner, RT Born,M Springer The Quantitative Methods Boot Camp: Teaching Quantitative Thinking and Computing Skills to Graduate Students in the Life Sciences

The Quantitative Methods Boot Camp: Teaching Quantitative Thinking and Computing Skills to Graduate Students in the Life Sciences

The past decade has seen a rapid increase in the ability of biologists to collect large amounts of data. It is therefore vital that research biologists acquire the necessary skills during their training to visualize, analyze, and interpret such data. To begin to meet this need, we have developed a “boot camp” in quantitative methods for biology graduate students at Harvard Medical School. The goal of this short, intensive course is to enable students to use computational tools to visualize…

R. Dutta Roy, M.I. Stefan, C. Rosenmund (2014) Biophysical properties of presynaptic short-term plasticity in hippocampal neurons: insights from electrophysiology, imaging and mechanistic models Front Cell Neurosci, 8: 141.

Biophysical properties of presynaptic short-term plasticity in hippocampal neurons: insights from electrophysiology, imaging and mechanistic models

Hippocampal neurons show different types of short-term plasticity (STP). Some exhibit facilitation of their synaptic responses and others depression. In this review we discuss presynaptic biophysical properties behind heterogeneity in STP in hippocampal neurons such as alterations in vesicle priming and docking, fusion, neurotransmitter filling and vesicle replenishment. We look into what types of information electrophysiology, imaging and mechanistic models have given about the time scales…

PLoS blog on Topic Pages

Expanding the Homepages of Knowledge

Back in 2012 PLOS Computational Biology began an experiment that aimed to combine the prestige and rigorous peer review associated with publishing in a scientific journal and the dynamic nature and easily accessible language of Wikipedia. Over two years and six articles later, today sees the launch of PLOS Computational Biology's Topic Pages Collection with the publication of the seventh Topic Page, "Multi-state Modeling of Biomolecules". Image Credit: PLOS Topic Pages aim to fill the gaps…

M.I. Stefan, S.J. Edelstein, N. Le Novère (2008) An allosteric model of calmodulin explains differential activation of PP2B and CaMKII PNAS, 105(31):10768-73.

An allosteric model of calmodulin explains differential activation of PP2B and CaMKII

Calmodulin plays a vital role in mediating bidirectional synaptic plasticity by activating either calcium/calmodulin-dependent protein kinase II (CaMKII) or protein phosphatase 2B (PP2B) at different calcium concentrations. We propose an allosteric model for calmodulin activation, in which binding to calcium facilitates the transition between a low-affinity [tense ( T )] and a high-affinity [relaxed ( R )] state. The four calcium-binding sites are assumed to be nonidentical. The model is…

M.I. Stefan, S.J. Edelstein, N. Le Novère (2009) Computing phenomenologic Adair-Klotz constants from microscopic MWC parameters BMC Syst Biol, 3(1):68.

Computing phenomenologic Adair-Klotz constants from microscopic MWC parameters

Modellers using the MWC allosteric framework have often found it difficult to validate their models. Indeed many experiments are not conducted with the notion of alternative conformations in mind and therefore do not (or cannot) measure relevant microscopic constant and parameters. Instead, experimentalists widely use the Adair-Klotz approach in order to describe their experimental data. We propose a way of computing apparent Adair-Klotz constants from microscopic association constants and…

S.J. Edelstein, M.I. Stefan, N. Le Novère (2010) Ligand depletion in vivo modulates the dynamic range and cooperativity of signal transduction PLoS ONE, 5(1): e8449.

Ligand Depletion in vivo Modulates the Dynamic Range and Cooperativity of Signal Transduction

Biological signal transduction commonly involves cooperative interactions in the binding of ligands to their receptors. In many cases, ligand concentrations in vivo are close to the value of the dissociation constant of their receptors, resulting in the phenomenon of ligand depletion. Using examples based on rotational bias of bacterial flagellar motors and calcium binding to mammalian calmodulin, we show that ligand depletion diminishes cooperativity and broadens the dynamic range of…

C. Li, M. Donizelli, N. Rodriguez, H. Dharuri, L. Endler, V. Chelliah, L. Li, E. He, A. Henry, M.I. Stefan, J.L. Snoep, M. Hucka, N. Le Novère, C. Laibe (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models BMC Syst Biol, 4:92.

BioModels Database: An enhanced, curated and annotated resource for published quantitative... - Europe PMC Article

Quantitative models of biochemical and cellular systems are used to answer a variety of questions in the biological sciences. The number of published quantitative models is growing steadily thanks to increasing interest in the use of models as well as the development of improved software systems and the availability of better, cheaper computer hardware. To maximise the benefits of this growing body of models, the field needs centralised model repositories that will encourage, facilitate and…

M.I. Stefan, D.P. Marshall, N. Le Novère (2012) Structural Analysis and Stochastic Modelling Suggest a Mechanism for Calmodulin Trapping by CaMKII PLoS ONE, 7(1): e29406.

Structural Analysis and Stochastic Modelling Suggest a Mechanism for Calmodulin Trapping by CaMKII

Activation of CaMKII by calmodulin and the subsequent maintenance of constitutive activity through autophosphorylation at threonine residue 286 (Thr286) are thought to play a major role in synaptic plasticity. One of the effects of autophosphorylation at Thr286 is to increase the apparent affinity of CaMKII for calmodulin, a phenomenon known as “calmodulin trapping”. It has previously been suggested that two binding sites for calmodulin exist on CaMKII, with high and low affinities…

L. Li, M.I. Stefan, N. Le Novère (2012) Calcium Input Frequency, Duration and Amplitude Differentially Modulate the Relative Activation of Calcineurin and CaMKII PLoS ONE, 7(9): e43810.

Calcium Input Frequency, Duration and Amplitude Differentially Modulate the Relative Activation of Calcineurin and CaMKII

NMDA receptor dependent long-term potentiation (LTP) and long-term depression (LTD) are two prominent forms of synaptic plasticity, both of which are triggered by post-synaptic calcium elevation. To understand how calcium selectively stimulates two opposing processes, we developed a detailed computational model and performed simulations with different calcium input frequencies, amplitudes, and durations. We show that with a total amount of calcium ions kept constant, high frequencies of…

M.I. Stefan, N. Le Novère (2013) Cooperative Binding. PLoS Comput Biol, 9(6): e1003106.

Cooperative Binding

Molecular binding is an interaction between molecules that results in a stable association between those molecules. Cooperative binding occurs if the number of binding sites of a macromolecule that are occupied by a specific type of ligand is a nonlinear function of this ligand's concentration. This can be due, for instance, to an affinity for the ligand that depends on the amount of ligand bound. Cooperativity can be positive (supralinear) or negative (infralinear). Cooperative binding is…