Christopher N. Rowley

Learn More
Genetic variants that modify brain gene expression may also influence risk for human diseases. We measured expression levels of 24,526 transcripts in brain samples from the cerebellum and temporal cortex of autopsied subjects with Alzheimer's disease (AD, cerebellar n=197, temporal cortex n=202) and with other brain pathologies (non-AD, cerebellar n=177,(More)
A multitude of biological processes requires the participation of specific cations, such as H, Na, K, Ca, and Mg. Many of these processes can take place only when proteins have the ability to discriminate between different ions with a very high fidelity. How this is possible is a fundamental question that has fascinated scientists for a long time. At the(More)
Antifreeze glycoproteins (AFGPs) are a unique class of proteins that are found in many organisms inhabiting subzero environments and ensure their survival by preventing ice growth in vivo. During the last several years, our laboratory has synthesized functional C-linked AFGP analogues (3 and 5) that possess custom-tailored antifreeze activity suitable for(More)
OBJECTIVE Recent genome-wide association studies (GWAS) of late-onset Alzheimer disease (LOAD) identified 9 novel risk loci. Discovery of functional variants within genes at these loci is required to confirm their role in Alzheimer disease (AD). Single nucleotide polymorphisms that influence gene expression (eSNPs) constitute an important class of(More)
The quantum mechanical (QM)/molecular mechanical (MM) interface between Chemistry at HARvard Molecular Mechanics (CHARMM) and TURBOMOLE is described. CHARMM provides an extensive set of simulation algorithms, like molecular dynamics (MD) and free energy perturbation, and support for mature nonpolarizable and Drude polarizable force fields. TURBOMOLE(More)
Electrophilic olefins can react with the S-H moiety of cysteine side chains. The formation of a covalent adduct through this mechanism can result in the inhibition of an enzyme. The reactivity of an olefin towards cysteine depends on its functional groups. In this study, 325 reactions of thiol-Michael-type additions to olefins were modeled using density(More)
Knowledge of the hydration structure of Na(+) and K(+) in the liquid phase has wide ranging implications in the field of biological chemistry. Despite numerous experimental and computational studies, even basic features such as the coordination number of these alkali ions in liquid water, thought to play a critical role in selectivity, continue to be the(More)
Leucine rich repeat transmembrane protein 3 (LRRTM3) is member of a synaptic protein family. LRRTM3 is a nested gene within α-T catenin (CTNNA3) and resides at the linkage peak for late-onset Alzheimer's disease (LOAD) risk and plasma amyloid β (Aβ) levels. In-vitro knock-down of LRRTM3 was previously shown to decrease secreted Aβ, although the mechanism of(More)
The high membrane permeability of H2S was studied using polarizable molecular dynamics simulations of a DPPC lipid bilayer. The solubility-diffusion model predicts permeability coefficients of H2S and H2O that are in good agreement with experiment. The computed diffusion coefficient profile shows H2S to diffuse at a lower rate than H2O, but the barrier for(More)
Molecular dynamics (MD) simulations using the Drude polarizable force field are used to study the solution and interfacial properties of hydrogen sulfide (H2S) in water. Pairwise H2O-H2S Lennard-Jones interactions were optimized to the experimental H2S gas solubility at 298 K. These parameters yield hydration free energies and diffusion coefficients for H2S(More)