James B Matthew

Learn More
Several different functions have been put forward for evaluating the energetics of ligand binding to proteins. Those employed in the DOCK, GOLD and FlexX docking programs have been especially widely used, particularly in connection with virtual high-throughput screening (vHTS) projects. Until recently, such evaluation functions were usually considered only(More)
Recent improvements in the understanding of electrostatic interactions in proteins serve as a focus for the general topic of pH-dependent processes in proteins. The general importance of pH-dependent processes is first set out in terms of hydrogen ion equilibria, stability, ligand interactions, assembly, dynamics, and events in related molecular systems.(More)
The solvent-accessibility-modified, Tanford-Kirkwood, discrete charge model for electrostatic effects is applied to both ribonuclease A and ribonuclease S. The behavior of individual titratable sites and the pH-dependent free energy of denaturation are correctly predicted. The use of the solvent-accessibility factor in reducing charge-site interactions(More)
Using recombinant DNA techniques, we have made a series of amino-terminal muteins of human interleukin-1 (IL-1). Two of the muteins demonstrated 4-7-fold increase in bioactivity as compared to that of the native IL-1. The enhanced biological potency coincides with an increase in both receptor binding affinity and in vivo tumor inhibitory activity. By site(More)
The principal component of normal adult human hemoglobin was equilibrated under various conditions with 13CO2. Quantitative analysis of the carbamino resonance intensities over the pH range of 6.5 to 9.0 shows that the effects of conversion from the deoxy to the liganded state in reducing the carbamino adduct formation occur predominantly at Val-1beta.(More)
A novel analytical method for comparing molecular shapes by optimizing the intersection of molecular "SKINS" has been developed. This method provides a quantitative measure of the shape similarity by maximizing the intersection volume of molecular surfaces with a finite thickness; a molecular skin. We report shape matching of a small tripeptide inhibitor(More)
Various studies have shown that reaction rates between reversibly binding electron transfer proteins depend strongly on solution ionic strength. These observations suggest that intermolecular electrostatic interactions are important in facilitating the formation of a productive reaction complex. A recently examined system involves the reduction of(More)
The static accessibility modified discrete charge model for electrostatic interactions in proteins is extended to the prediction of the pH dependence of hydrogen exchange reactions. The exchange rate profiles of buried amide protons are shown to follow the calculated pH dependence of the electrostatic component of protein stability. Rate profiles are(More)