Simulation Studies of Protein-Ligand Interactions

Conference paper
Part of the Lecture Notes in Computational Science and Engineering book series (LNCSE, volume 4)


Protein-ligand interactions control a majority of cellular processes and are the basis of many drug therapies. First, this paper summarizes experimental approaches used to characterize the interactions between proteins and small molecules: equilibrium measurement of binding constant and standard free energy of binding and the dynamic approach of ligand extraction via atomic force microscopy. Next, the paper reviews ideas about the origin of different component terms that contribute to the the stability of protein-ligand complexes. Then, theoretical approaches to studying protein-small molecule interactions are addressed, including forced extraction of ligand and perturbation methods for calculating potentials of mean force and free energies for molecular transformation. Last, these approaches are illustrated with several recent studies from our laboratory: (1) binding of water in cavities inside proteins, (2) calculation of binding free energy from “first principles” by a new application of molecular transformation, and (3) extraction of a small ligand (xenon) from a hydrophobic cavity in mutant T4-lysozyme L99A.


Free Energy Free Energy Change Ligand Molecule Standard Free Energy Solvation Free Energy 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  1. 1.Department of Biochemistry and Biophysics, School of MedicineUniversity of North CarolinaChapel HillUSA

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