TAMD is a collective-variable method in which the efficiency of sampling of CV space is enhanced by providing thermal noise to slow auxiliary variables that live in CV space, but are tethered to configuration space via the CV mapping functions.

The String Method in Collective Variables aims to identify minimum free-energy pathways (MFEPs) in a specified collective-variable space. Our implementation uses replicas of an MD system, each tethered to a discrete point along a putative path, and mean forces on those points orthogonal to the local path tangent result in their motion. Motion stops when orthogonal forces vanish.

The central idea of TAMD is that the auxiliary variables move on the free-energy surface as if it were a potential-energy surface; i.e., at any temperature we like. The instantaneous forces acting on the auxiliary variables approximate, when averaged, free-energy gradients. OTFP is a method by which we can collect these samples and use them in an optimization scheme to compute the parameters of a free-energy function. By invoking the form of a basis-function expansion, we end up using linear algebra to find the parameters as the coefficients of this expansion.

In Markovian Milestoning, we run MD simulations restricted to cells in CV space by reflecting boundary conditions. The cells are distributed along pathways connecting basins, and statistics on boundary collisions and escape attempts for each cell individually are collected and allow for self-consistent determination of cell occupancy probabilities and mean first-passage times along the pathway.

gp120

gp120 is the element of the heterotrimeric (gp120-gp41)₃ Env spike that recognizes CD4 and initializes the fusion machinery of HIV-1.

gp41

gp41 anchors the trimeric (gp120-gp41)₃ Env spike to viral membrane. It is required for fusion, but its exact roles are not well understood.

Small-Molecule CD4 Mimetics

In collaboration with groups from Dana Farber Cancer Institute, Columbia University, Yale University, University of Montreal, and Drexel College of Medicine, we use computational tools to design and optimize small molecules that bind in the Phe43 cavity of HIV-1 gp120.

Virolytic Entry Inhibitors

In collaboration with UPenn and the Drexel College of Medicine, we have developed a new class of virolytic inhibitors that seem to act by triggering the fusion cascade of Env.

Epoxy-Amines

The reaction of di-, tri-, and tetra-epoxidized monomers with polyamine crosslinkers is a popular thermosetting chemistry. Thermomechanical properties can be tuned over wide ranges independently via judicious choices of monomer chemistries and stoichiometries. We conduct MD simulations of model epoxy-amine thermosets to test ideas for creating such structure-function relationships.

Vinyl ester thermoset resins

Vinyl ester resins are a class of thermosets that rely on polymerization of carbon-carbon double bonds. Small molecular weight monomers, like styrene, normally polymerize to form thermoplastics; adding a small amount of species with two or more double bonds per molecules leads to crosslinking of the linear polymers.

Biological Membranes

A triple-junction (3-j) in a bilayer system is a unique defect required to form a hemifusion diaphragm (HD). Using coarse-grained MD, we study several aspects of HD's; this image is an axisymmetric density field showing a stable HD from a 500-ns MD simulation.

Complex Fluids

12-hydroxystearic acid (12HSA), when optically pure, assembles into chiral, fibrillar structures. We investigate the possible nucleation events of this assembly using MD simulations.