Full Description
Free energy calculations represent the most accurate computational method available for predicting enzyme inhibitor binding affinities. Advances in computer power in the 1990s enabled the practical application of these calculations in rationale drug design. This book represents the first comprehensive review of this growing area of research and covers the basic theory underlying the method, numerous state of the art strategies designed to improve throughput and dozen examples wherein free energy calculations were used to design and evaluate potential drug candidates.
Contents
1. Historical Overview and Future Challenges; J.A. McCammon. Section One: Theory. 2. Free Energy Calculations: Methods for Estimating Ligand Binding Affinities; D.A. Pearlman. 3. Molecular Mechanics Force Field Development and Applications; P.M. Todebush, J.P. Bowen. Section Two: Molecular Properties. 4. Solvation Thermodynamics and the Treatment of Equilibrium and Nonequilibrium Solvation Effects by Models Based on Collective Solvent Coordinates; C.J. Cramer, D.G. Truhlar. 5. Relative Solvation Free Energies Calculated Using Explicit Solvent; A. Agarwal, et al. 6. Tautomerism and Ionisation Studies Using Free Energy Methods; G.A. Worth, P.M. King. Section Three: Ligand Binding. 7. Free Energy Calculations on Enzyme-Inhibitor Complexes: Studies of Thermolysin and Rhizopus Pepsin; B.G. Rao. 8. Free Energy Calculations on DNA: Ligand Complexes; S.B. Singh, P.A. Kollman. Section Four: Ligand Design and Analysis. 9. The Linear Interaction Energy Method for Computation of Ligand Binding Affinities; J. Åqvist, J. Marelius. 10. New Free Energy Based Methods for Ligand Binding from Detailed Structure-Function to Multiple-Ligand Screening; S. Banba, et al. 11. Ligand Interaction Scanning Using Free Energy Calculations; M.D. Erion, M.R. Reddy. 12. MM-PBSA Applied to Computer-Assisted Ligand Design; B. Kuhn, et al. 13. Reaction Free Energy Profiles Using Free Energy Perturbation and Coordinate Coupling Methodologies: Analysis of the Dihydrofolate Reductase Catalytic Mechanism; U.C. Singh, et al. Section Five: Drug Design Case Studies. 14. Fructose 1,6-Bisphosphatase: Use of Free Energy Calculations in the Design and Optimization of AMP Mimetics; M.R. Reddy, M.D. Erion. 15. COX-2, SRC SH2 Domain, HIV Reverse Transcriptase, and Thrombin: Computational Approaches to Protein-Ligand Binding; W.L. Jorgensen, et al. 16. HIV-1 Protease: Structure-Based Drug Design Using the Free Energy Perturbation Approach; M.R. Reddy, K. Appelt. 17. Thymidylate Synthase: Free Energy Calculations for Estimating Inhibitor Binding Affinities; T.-S. Lee, P.A. Kollman. 18. Dihydrofolate Reductase: Free Energy Calculations for the Design of Mechanism-Based Inhibitors; J.E. Gready, P.L. Cummins. 19. Adenosine Deaminase: Calculation of Relative Hydration Free Energy Differences; M.D. Erion, M.R. Reddy. Index.
