Weighted Ensemble of Pathways for Ligand Unbinding from T4 Lysozyme

Ligand Unbinding from the Estrogen Receptor;

Purification of Bacteriophage T4 Lysozyme*

The lysozyme of bacteriophage T4 was purified to apparent homogeneity from lysates of the phage grown on Escherichia coli. The enzyme is a single polypeptide chain of molecular weight 19,000, with a single NH&erminal methionine residue and a single COOH-terminal leuciue residue. The amino acid composition of the protein was determined. The phage lysozyme exhibits a much greater specific activit...

The three dimensional structure of the lysozyme from bacteriophage T4.

The three dimensional structure of the lysozyme from bacteriophage T4 has been determined from a 2.5 A resolution electron density map. About 60% of the molecule is in a helical conformation and there is one region consisting of antiparallel beta-structure. The polypeptide backbone folds into two distinct lobes linked in part by a long helix. In the region between the two lobes, there is a clef...

Conformational selection and adaptation to ligand binding in T4 lysozyme cavity mutants.

The studies presented here explore the relationship between protein packing and molecular flexibility using ligand-binding cavity mutants of T4 lysozyme. Although previously reported crystal structures of the mutants investigated show single conformations that are similar to the WT protein, site-directed spin labeling in solution reveals additional conformational substates in equilibrium exchan...

Kinetics of protein-ligand unbinding: Predicting pathways, rates, and rate-limiting steps.

The ability to predict the mechanisms and the associated rate constants of protein-ligand unbinding is of great practical importance in drug design. In this work we demonstrate how a recently introduced metadynamics-based approach allows exploration of the unbinding pathways, estimation of the rates, and determination of the rate-limiting steps in the paradigmatic case of the trypsin-benzamidin...