Biomedical subjects

Michael F Hagan

Publications and source records attributed to Michael F Hagan.

3 recordsLinked to original sources

PubMed2006

Dynamic pathways for viral capsid assembly.

We develop a class of models with which we simulate the assembly of particles into T1 capsidlike objects using Newtonian dynamics. By simulating assembly for many different values of system parameters, we vary the forces that drive assembly. For some ranges of parameters, assembly is facile; for others, assembly is dynamically frustrated by kinetic traps corresponding to malformed or incompletely formed capsids. Our simulations sample many independent trajectories at various capsomer concentrations, allowing for statistically meaningful conclusions. Depending on subunit (i.e., capsomer) geometries, successful assembly proceeds by several mechanisms involving binding of intermediates of various sizes. We discuss the relationship between these mechanisms and experimental evaluations of capsid assembly processes.

Capsid↗

PubMed2004

Hybridization dynamics of surface immobilized DNA.

We model the hybridization kinetics of surface attached DNA oligomers with solubilized targets. Using both master equation and rate equation formalisms, we show that, for surface coverages at which the surface immobilized molecules interact, barriers to penetration create a distribution of target molecule concentrations within the adsorbed layer. By approximately enumerating probe and target conformations, we estimate the probability of overlap between complementary probe and target regions as a function of probe density and chain length. In agreement with experiments, we find that as probe molecules interact more strongly, fewer nucleation sites become accessible and binding rates are diminished relative to those in solution. Nucleation sites near the grafted end of the probes are least accessible; thus targets which preferentially bind to this region show more drastic rate reductions than those that bind near the free end of the probe. The implications of these results for DNA-based biosensors are discussed.

Adsorption↗

PubMed2003

Atomistic understanding of kinetic pathways for single base-pair binding and unbinding in DNA.

We combine free-energy calculations and molecular dynamics to elucidate a mechanism for DNA base-pair binding and unbinding in atomic detail. Specifically, transition-path sampling is used to overcome computational limitations associated with conventional techniques to harvest many trajectories for the flipping of a terminal cytosine in a 3-bp oligomer in explicit water. Comparison with free-energy projections obtained with umbrella sampling reveals four coordinates that separate true dynamic transition states from stable reactant and product states. Unbinding proceeds via two qualitatively different pathways: one in which the flipping base breaks its intramolecular hydrogen bonds before it unstacks and another in which it ruptures both sets of interactions simultaneously. Both on- and off-pathway intermediates are observed. The relation of the results to coarse-grained models for DNA-based biosensors is discussed.

Base Pairing↗