CAREER: Modeling and Analyzing High-Dimensional Molecular Assembly: Quantifying the Impact of Allergen Structure

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This CAREER award will integrate research and education dedicated to computational simulation and analysis of molecular interactions. Molecular interactions and binding are critical to the construction of functional superstructures. One such process, molecular assembly of antibodies and allergens is a precursor to signaling allergic response. This project will study how to efficiently capture and analyze the complex conformational space of multi-molecular binding, with the goal to provide detailed information about the structure and assembly of aggregates. The method, inspired by high-dimensional robotic motion search, will incorporate and integrate hybrid and multi-resolution models of molecular structures, motion planning simulation for assembly pathways and kinetics, and understanding of the impact of allergen structure and antigen assembly. This work will develop tools that are applicable to a range of molecular assembly problems. Geometric insights provided by modeling will enable the rapid testing of disruptions to assembly-induced allergenic signaling, i.e., allergy treatments. Experimental collaborations will allow direct utilization and verification of models and tools, and rapid simulation may point the way to new experiments. The educational plan includes development of a molecular assembly haptic interaction for demonstrating molecular interaction and the design of cross-disciplinary educational materials.This CAREER will integrate research and education dedicated to the computational simulation and analysis of assembly processes. This will be achieved through four research thrusts that lead to a tunable-resolution, computationally-efficient, generic framework for the structural modeling and analysis of molecular assembly based on techniques in biophysics, planning, and stochastic processes. The focus of this award will be simulation and analysis of antibody-allergen interaction. A tunable resolution model is required that will enable low computational cost simulations achieved through limited, yet realistic, molecular flexibility and hybrid-resolution structures. The proposed research focuses on adaptations of polygon-based models used in preliminary work, and autonomous targeted placements of kinematic linkages to enable flexibility. To enable simulation and kinetics analysis of assembly processes, new heuristics will be designed and integrated into data structure shown capable of simulating motions in high-dimensional conformational spaces. Geometric insights provided by modeling will enable the rapid testing of disruptions to the allergenic cascade, thus leading to allergy treatments. Experimental collaborations will allow direct utilization and verification of the proposed work and may lead to the development of new experiments. In addition, an educational haptic m0olecular assembly module will permit students to perceive physically the atomic forces between two interacting molecules. This is coupled with interdisciplinary research and new courses, with an emphasis on the integration of underrepresented minorities in the research.