Biomedical subjects

Noel T Southall

Publications and source records attributed to Noel T Southall.

3 recordsLinked to original sources

PubMed2006

Kinase patent space visualization using chemical replacements.

Here we present a methodology for characterizing the structure of patented chemical space. This approach identifies those chemical replacements that can connect sets of exemplified compounds in individual patents. Chemists can then search these replacements to help them discover the architecture within their patent space of interest. To demonstrate the utility of such an approach, we characterize a set of kinase inhibitors from patents and literature and find that many companies' patents can be understood to be straightforward modifications of competitors' patents. By reapplying these same chemical themes to other related compound series, novel, biologically active compounds can be discovered.

Databases, Factual↗

PubMed2002

Potential of mean force between two hydrophobic solutes in water.

We study the potential of mean force between two nonpolar solutes in the Mercedes Benz model of water. Using NPT Monte Carlo simulations, we find that the solute size determines the relative preference of two solute molecules to come into contact ('contact minimum') or to be separated by a single layer of water ('solvent-separated minimum'). Larger solutes more strongly prefer the contacting state, while smaller solutes have more tendency to become solvent-separated, particularly in cold water. The thermal driving forces oscillate with solute separation. Contacts are stabilized by entropy, whereas solvent-separated solute pairing is stabilized by enthalpy. The free energy of interaction for small solutes is well-approximated by scaled-particle theory.

Monte Carlo Method↗

PubMed2002

How ions affect the structure of water.

We model ion solvation in water. We use the MB model of water, a simple two-dimensional statistical mechanical model in which waters are represented as Lennard-Jones disks having Gaussian hydrogen-bonding arms. We introduce a charge dipole into MB waters. We perform (NPT) Monte Carlo simulations to explore how water molecules are organized around ions and around nonpolar solutes in salt solutions. The model gives good qualitative agreement with experiments, including Jones-Dole viscosity B coefficients, Samoilov and Hirata ion hydration activation energies, ion solvation thermodynamics, and Setschenow coefficients for Hofmeister series ions, which describe the salt concentration dependence of the solubilities of hydrophobic solutes. The two main ideas captured here are (1) that charge densities govern the interactions of ions with water, and (2) that a balance of forces determines water structure: electrostatics (water's dipole interacting with ions) and hydrogen bonding (water interacting with neighboring waters). Small ions (kosmotropes) have high charge densities so they cause strong electrostatic ordering of nearby waters, breaking hydrogen bonds. In contrast, large ions (chaotropes) have low charge densities, and surrounding water molecules are largely hydrogen bonded.

Computer Simulation↗