Research Abstract:
Our research uses the methods of theoretical and computational science to study the physical phenomena underlying the behavior of biological systems. Such studies offer insight into the basic mechanisms of biomolecular dynamics and function and provide a foundation for new tools and algorithms to complement experimental research.
Understanding biomolecular solvation. The properties of biomolecules are strongly affected by their surrounding aqueous and ionic environment. Our research in solvation focuses on the development and application of accurate continuum solvent models for biomolecules. First, we continue to develop the APBS and PDB2PQR software packages which implement Poisson-Boltzmann electrostatics and various nonpolar models of continuum solvation. Second, we are working on improved continuum models for biomolecular solvation. Finally, we are developing multiscale treatments of solvation with particular emphasis on the influence of ionic species on nucleic acid structure and dynamics.
Allostery and energy flow in biomolecules. Proteins communicate information (e.g., ligand binding, etc.) over large distances through mechanisms that are often poorly understood. We are employing both bioinformatic and biophysical simulation techniques to study the molecular foundations of allosteric communication in protein systems. Initial work is focused on the NikR protein, a regulatory protein found in several bacteria species, and thrombin, an essential component in the blood clotting cascade.
Small molecule effects on biomembrane electrostatics and mechanics. We are interested in the ability of small molecules to perturb the electrical and mechanical properties of biological membranes. The mechanism of this perturbation is not well understood but has a significant impact on membrane channel function and cellular electrophysiology. Initial studies on salicylate, have revealed interesting mechanisms for its effects on membrane electrostatics and mechanics. We are now broadening these studies to examine other amphiphilic molecules known to affect membrane capacitance, bending modulus, and electrostatic potential.
Nanotechnology-based cancer therapeutics. We are part of the Siteman Cancer Center for Nanotechnology Excellence effort to develop nanoparticle-based technology for the delivery of therapeutic and diagnostic chemicals in a selective and efficient manner. One aspect of our research in this area is the development of databases, vocabularies, and ontologies to describe the physical and functional properties for a variety of nanoparticle platforms. A second area of research is the development of multiscale simulations for understanding the mechanism of nanoemulsion function and interaction with lipid membranes.
Selected Publications:
Dolinsky TJ, Czodrowski P, Li H, Nielsen JE, Jensen JH, Klebe G, Baker NA. PDB2PQR: Expanding and upgrading automated preparation of biomolecular structures for molecular simulations. Nucleic Acids Res 2007 35:W522-525 .
Wagoner JA, Baker NA. Assessing implicit models for nonpolar mean solvation forces: the importance of dispersion and volume terms. Proc Natl Acad Sci USA 2006 103:8331-8336.
Song Y, Guallar V, Baker NA. Molecular dynamics simulations of salicylate effects on the micro- and mesoscopic properties of a dipalmitoylphosphatidylcholine bilayer. Biochemistry 2005 44:13425-13438.
Baker NA. Improving implicit solvent simulations: a Poisson-centric view. Curr Opin Struct Biol 2005 15:137-143.
Song Y, Zhang Y, Bajaj CL, Baker NA. Continuum diffusion reaction rate calculations of wild type and mutant mouse acetylcholinesterase: adaptive finite element analysis. Biophys J 2004 87:1558-1566.
Last Updated: 09/12/2007 |