An algorithm for planning collision-free paths among polyhedral obstacles
Communications of the ACM
Proceedings of the sixth annual international conference on Computational biology
A Motion Planning Approach to Flexible Ligand Binding
Proceedings of the Seventh International Conference on Intelligent Systems for Molecular Biology
Complexity of the mover's problem and generalizations
SFCS '79 Proceedings of the 20th Annual Symposium on Foundations of Computer Science
Simulating protein motions with rigidity analysis
RECOMB'06 Proceedings of the 10th annual international conference on Research in Computational Molecular Biology
Hi-index | 0.00 |
IgE antibodies bound to cell-surface receptors, FceRI, crosslink through the binding of antigens on the cell surface. This formation of aggregates is what simulates mast cells and basophils in order to initiate an allergic response. Experimental studies have shown that the spatial organization of aggregated IgE-FcεRI complexes affect transmembrane signaling that initiate these responses. About 1,500 Americans die each year from anaphylatic shock caused by these aggregations. The methods we present in this paper address modeling and analyzing this critical molecular data. First, we developed 3D models of a trivalent antigen and IgE-FceRI complex binding using relaxed constraints. Simplified models were generated from all-atom structures to reduce the complexity of the geometry and are simulated on a plane to capture movement of antibodies on the cell surface. This reduces the computational complexity of the simulation to a rigid body problem, often addressed in motion planning. Motions and resulting aggregations are extracted from Monte Carlo simulations with kinetic rates derived from experiments. In order to analyze the resulting structures, we introduce techniques to map 3D molecular binding to a graph structure. This facilitates analysis of aggregate structures because simple graph metrics, such as connected components and subgraph isomorphism, can be used to quickly quantify and analyze aggregate structure.