MD-based Energetic Heat Kernel Analysis: Insights to PDZ Allosterism

Benjamin Cowan
Benjamin Cowan

Ben Cowan is a rising senior (22′) from Lower Merion Pennsylvania majoring in Neuroscience and the College of Integrative Sciences. In his free time, Ben enjoys coding, doing graphic design, 3D and generative art, making and listening to music, skateboarding, and reading philosophy. After Wesleyan Ben hopes to pursue graduate studies in computational neuroscience.

Abstract: Allosteric long-range interactions which characterize the conformational and energetic dynamics of many protein systems such as PDZ-domain containing systems proves an important focus in many forms of molecular dynamics (MD) research for understanding the dynamics underlying protein interaction and potential drug delivery pathways. A sector-based analysis identifies a network of residues referred to as a “sector” significantly involved in protein allostery. PDZ allosterism has been investigated through both a coevolutionary lens and with more recent MD-sector based approach, a residue-pairwise motionally-covariant lens. Although the importance of conformational change has been demonstrated to be important in understanding PDZ-domain dynamics, evidence of dynamic allosteric activity in PDZ-based systems, allosterism in the absence of macromolecular conformational change, also point towards the importance of energetic approaches. In the present project, we use a novel energetic analysis to investigate the role of energetic pathways within CRIB-par6 allostery by analyzing electrostatic interactions temporally embedded over the course of a MD-simulation. In conjunction with a motional dynamics approach endowed by MD-sector analysis towards PDZ allosterism, the present analysis aims to investigate the energetic dynamics between protein residues at atomic resolution for the PDZ containing CRIB-Par6 system.


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