Professor
Department of Physiology
School of Medicine

twoolf@jhu.edu

204 Biophysics Building
725 N. Wolfe Street
Baltimore, MD 21205

Office: 410-614-2643
Lab: 410-614-4435

We believe that one of the next scientific frontiers is represented by a fuller understanding of the roughly one-quarter of the genome devoted to membrane proteins. This rapidly growing branch of bio-informatics, that includes computational biophysics, represents the main research direction of our group.

The research directions of the group thus aim to provide insight into critical issues for membrane systems. In pursuit of these goals, we use extensive computer calculations to build an understanding of the relations between microscopic motions and the world of experimental measurements. Our calculations utilize our own Beowulf computer cluster as well as national supercomputer centers. An especially strong focus has been on the computed motions of proteins and all-atom models of the lipid bilayers that mediate their influence. To compute these motions we use the molecular dynamics program CHARMM. We hope to use our understanding of the molecular motions for the prediction of membrane protein structures using new computational methods.

The lab is currently focused on four main areas: 1) Detailed all-atom models of protein:lipid interactions as seen through model systems: e.g. single alpha-helices and the alpha-helical homodimer glycophorin; 2) Specific lipid recognition as seen in the fatty acid binding proteins and their close relatives the retinol binding proteins; 3) Calculation of reaction rates and reaction paths within model systems and the extension of these ideas to larger protein systems; and 4) Prediction of alpha-helical membrane protein tertiary structures through hierarchical modeling of helix interactions and the development of implicit solvent representations for the lipid bilayer.

All of these projects have experimental connections. For example, the first project is related to the experimental work in the labs of Antoinette Killian (Netherlands) and Don Engelman (Yale University). The second project is related to structural work in the groups of Len Banaszak (University of Minnesota), James Sacchettini (Albert Einstein), and David Cistola (Washington University) and to thermodynamic work in the lab of Alan Kleinfeld (MBI, La Jolla).

Selected Publications
Weathers, E.A., M.E. Paulaitis, T.B. Woolf and J.H. Hoh. 2004. Reduced amino acid alphabet is sufficient to accurately recognize intrinsically disordered protein. FEBS Lett. 576:348-352.

Jang, H., P.S. Crozier, M.J. Stevens, and T.B. Woolf. 2004. How environment supports a state: Molecular dynamics simulations of two states in bacteriorhodopsin suggest lipid and water compensation. Biophys. J. 87:129-145.

Sachs, J.N., H. Nanda, H.I. Petrache, and T.B. Woolf. 2004. Changes in phosphatidylcholine headgroup tilt and water order induced by monovalent salts: Molecular dynamics simulations. Biophys. J. 86:3772-3782.

Lu, N., Wu D., Woolf T.B. and Kofke D.A. 2004. Using overlap and funnel sampling to obtain accurate free energies from non-equilibrium work measurements. Phys. Rev. E. 69:Article #057702.

Stevens, M.J., J.H. Hoh, and T.B. Woolf. 2003. Insights into the molecular mechanism of membrane fusion from simulation: Evidence for the association of splayed tails. Phys. Rev. Lett. 91:Article #188102.

Crozier, P.S., M.J. Stevens, L.R. Forrest, and T.B. Woolf. 2003. Molecular dynamics simulation of dark-adapted rhodopsin in an explicit membrane bilayer: Coupling between local retinal and larger scale conformational change. J. Mol. Biol. 333:493-514.