User:Jamesef: Difference between revisions
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==James Fitzgerald== | ==James Fitzgerald== | ||
I am an undergraduate majoring in physics and mathematics. I work on computational and theoretical aspects of protein folding with Professors Tobin Sosnick[http://openwetware.org/wiki/Sosnick_Lab] and Karl Freed[http://home.uchicago.edu/~freed/]. | I am an undergraduate majoring in physics and mathematics. I work on computational and theoretical aspects of protein folding with Professors Tobin Sosnick[http://openwetware.org/wiki/Sosnick_Lab] and Karl Freed[http://home.uchicago.edu/~freed/]. My research is currently supported by the Arnold and Mable Beckman Foundation. | ||
'''Past Research''' | '''Past Research''' | ||
*My primary research interest has been the dynamics of proteins. My first project was to investigate the fundamental local motions of proteins. Through numerous simulations we find a fundamental anticorrelation between the motions of the phi torsion angle of the ith residue and the psi angle of the (i-1)st residue. This motion is accomplished through the rocking of the rigid peptide group. This motion is independent of solvent model, force field, and is seen both in the presence and absence of long range interactions. This fundamentally local motion is robust enough to describe both equilibrium fluctuations of the backbone and basin transitions. No longer range correlations are necessary in either type of motion to retain the global structure of the peptide. | *My primary research interest has been the dynamics of proteins. My first project was to investigate the fundamental local motions of proteins. Through numerous simulations we find a fundamental anticorrelation between the motions of the phi torsion angle of the ith residue and the psi angle of the (i-1)st residue. This motion is accomplished through the rocking of the rigid peptide group. This motion is independent of solvent model, force field, and is seen both in the presence and absence of long range interactions. This fundamentally local motion is robust enough to describe both equilibrium fluctuations of the backbone and basin transitions. No longer range correlations are necessary in either type of motion to retain the global structure of the peptide. A manuscript of this work has been accepted at the journal Biochemistry pending minor revisions. | ||
*In addition to my work with protein dynamics, I have considered the energetic and entropic content of protein sidechains. Using the information learned in this process I have developed new energy functions for use in computational studies of proteins. These energy functions use statistical mechanical concepts to relate statistics compiled from known protein crystal structures to the energy of a protein conformation. The correct expression for this energy requires many-body interactions. However, for computational simplicity we assume that energies are pair-wise additive and depend only on the distances between pairs of atoms. This assumption is obvisouly incorrect, and in order to diminish the associated errors, we introduce additional conditional dependences to implicitly reproduce these many body effects. Using these considerations, several energy functions are produced which only explicitly include pair-interactions between the protein backbone atoms and a single side-chain atom (the beta-carbon). However, even in this reduced representation they perform better than the best known all-atom energy function based upon their ability to distinguish native from non-native structures (average performance on 306 different decoys sets). I have also built the all-atom versions of these potentials which work even better than the reduced potentials. All potentials are currently in the optimization stage in order to be used for protein structure prediction and structure refinement. A manuscript describing this work is in preparation. | |||
'''Current Research''' | '''Current Research''' | ||
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*More recently I have been studying the fundamental motions of proteins by investigating topological constraints in protein folding. Using a mixture of differential geometry and computer simulations, I have suggested an equation of constraint which I suspect is respected in certain conformational transitions of proteins. The validity of this theory is being tested with a variety of computer simulations. | *More recently I have been studying the fundamental motions of proteins by investigating topological constraints in protein folding. Using a mixture of differential geometry and computer simulations, I have suggested an equation of constraint which I suspect is respected in certain conformational transitions of proteins. The validity of this theory is being tested with a variety of computer simulations. | ||
* | *Implicit and explicit solvent models for studying proteins sometimes give strikingly different results. I am studying these two methods to clearly dilineate these simularities and differences. | ||
{{SosnickLab}} | {{SosnickLab}} | ||
Revision as of 14:53, 29 September 2006
James Fitzgerald
I am an undergraduate majoring in physics and mathematics. I work on computational and theoretical aspects of protein folding with Professors Tobin Sosnick[1] and Karl Freed[2]. My research is currently supported by the Arnold and Mable Beckman Foundation.
Past Research
- My primary research interest has been the dynamics of proteins. My first project was to investigate the fundamental local motions of proteins. Through numerous simulations we find a fundamental anticorrelation between the motions of the phi torsion angle of the ith residue and the psi angle of the (i-1)st residue. This motion is accomplished through the rocking of the rigid peptide group. This motion is independent of solvent model, force field, and is seen both in the presence and absence of long range interactions. This fundamentally local motion is robust enough to describe both equilibrium fluctuations of the backbone and basin transitions. No longer range correlations are necessary in either type of motion to retain the global structure of the peptide. A manuscript of this work has been accepted at the journal Biochemistry pending minor revisions.
- In addition to my work with protein dynamics, I have considered the energetic and entropic content of protein sidechains. Using the information learned in this process I have developed new energy functions for use in computational studies of proteins. These energy functions use statistical mechanical concepts to relate statistics compiled from known protein crystal structures to the energy of a protein conformation. The correct expression for this energy requires many-body interactions. However, for computational simplicity we assume that energies are pair-wise additive and depend only on the distances between pairs of atoms. This assumption is obvisouly incorrect, and in order to diminish the associated errors, we introduce additional conditional dependences to implicitly reproduce these many body effects. Using these considerations, several energy functions are produced which only explicitly include pair-interactions between the protein backbone atoms and a single side-chain atom (the beta-carbon). However, even in this reduced representation they perform better than the best known all-atom energy function based upon their ability to distinguish native from non-native structures (average performance on 306 different decoys sets). I have also built the all-atom versions of these potentials which work even better than the reduced potentials. All potentials are currently in the optimization stage in order to be used for protein structure prediction and structure refinement. A manuscript describing this work is in preparation.
Current Research
- More recently I have been studying the fundamental motions of proteins by investigating topological constraints in protein folding. Using a mixture of differential geometry and computer simulations, I have suggested an equation of constraint which I suspect is respected in certain conformational transitions of proteins. The validity of this theory is being tested with a variety of computer simulations.
- Implicit and explicit solvent models for studying proteins sometimes give strikingly different results. I am studying these two methods to clearly dilineate these simularities and differences.
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