(3bs) Targeting Molecular Simulation Tools Toward Bioengineering Applications

The general motivation behind my research interests is a desire to find ways of harnessing the full capabilities of biomolecules as bioengineering tools.  The majority of my research work has focused on the development and validation of protein simulation methods used to address fundamental challenges in bioengineering.  My initial research focus was on nuclear magnetic resonance investigations of modified DNA structures for the purpose of elucidating the nature of their interactions with, and recognition by, various enzymes.  This early experimental work was supplemented by molecular simulation, which has proved to be the most powerful and productive research tool currently available for nanoscale structural studies.  Therefore, to quickly advance my studies of biomolecules as bioengineering tools, I transitioned to purely computational research efforts.  This work has included studies of a variety of wild-type and engineered biomolecules used as, or in the presence of, bioengineered structures.  Recently, my research has included a previously unexplored comparison of molecular dynamics force fields as used in the simulation of peptide and protein adsorption to material surfaces.  Most recently, I have begun the development of new simulation tools that will enable the study of complex structural properties proteins and the mechanisms underlying protein function.

As an independent investigator, I expect to continue my work focused on the use of biomolecules as bioengineering tools with particular emphasis on the development and evaluation of purpose-built biomolecular structures.  This work will be divided amongst the development of new computational research tools, studies of engineered biomolecules, and studies of the interactions between biomolecules and material surfaces.  The nature of this work dictates regular collaboration with researchers focusing on experimental techniques, so my research will provide a variety of opportunities for collaboration.  Through my research and teaching, I hope to engage students with diverse educational backgrounds in ways that will take advantage of their existing competencies and push them in the direction of developing new ones that will be needed soon in their research careers.  I have a great deal of coursework development and teaching experience, as well as experience with mentoring graduate and undergraduate students.

During this poster session, in addition to welcoming the discussion of my qualifications as a new faculty candidate, I will present details of my work in developing simulation tools for the study of allosteric pathways in proteins.  A brief overview of this project is included below.

Allosteric regulation of protein function is a mechanism by which a structural event occurring at one site within a protein’s overall structure causes an effect at another site, and allostery plays a central role in a huge variety of mechanistic pathways in biological systems.  The prediction and modulation of allosteric responses in proteins holds promise for applications in a diverse range of research areas, including drug design and materials engineering.  The structural changes involved in protein allostery include deformations where local elastic moduli play a major role.  Knowledge of the elastic modulus at each atom position or within specific regions in a protein can provide valuable information about the local mobility and stability under conformational deformations.  However, most methods used for calculating local elastic moduli cannot be applied to proteins in a straightforward manner because they require second derivatives of the potentials that describe the interactions amongst a protein's atoms.  To address this issue, I have begun the development of computational methods that enable the measurement of elastic moduli at different positions in a protein in order to build a 3D map of local mechanical properties that can be used to identify pathways of allostery in proteins and protein networks.  Presented here are the results from a preliminary set of protein structural analyses completed using these methods to calculate elastic moduli in an atomistic fashion.