Binding affinity calculation

Zhou, R. Friesner, R.A. Ghosh, A. Rizzo, R.C. Jorgensen, W.L. Levy, R.M., New linear interaction method for binding affinity calculations using a continuum solvent model, J. Phys. Chem. B 2001,105,10388-10397... 

Zhou, Z., Bates, M., Madura, J.D. Structure modeling, ligand binding, and binding affinity calculation (LR-MM-PBSA) of human heparanase for inhibition and drug design. Proteins 2006, 65, 580-92. 

The calculation of the binding affinity with con.sidcration of all tbc.se effects for virtual screening is not possible. In order to circumvent thus difficulty, scoring functions arc used instead, c.g., the Liidi scoring function [80, or consensus scoring functions derived from FlevX score, DOCK score, GOLD score, ChemScore, or PMF score [81 ]. 

Fig. 11.6 The SC24/halide system. (Figure adapted from Lybrand T P, ] A McCammon and G Wipff 1986. Theoretical Calculation of Relative Binding Affinity in Host-Guest Systems. Proceedings of the National Al adeniy of Sciences USA 83 833-835.)...

FIGURE 2.4 Occupancy-response curves for P-adrenoceptor agonists in transfected CHO cells. Occupancy (abscissae) calculated from binding affinity measured by displacement of [125I]iodocyanopindolol. Response measured as increases in cyclic AMP. Drawn from [3],... 

Reddy MR, Erion MD, Agarwal A. Free energy calculations Use and limitations in predicting ligand binding affinities. In Lipkowitz KB, Boyd DB, editors. Reviews in Computational Chemistry, Vol. 16. New York Wiley-VCH, 2000. p. 217-304. 

It has been argued that using several A parameters A0, A(,. .., L one can perform several mutation studies simultaneously in so-called competitive binding experiments [57]. This approach allows the calculation of AAy for any two ligands and rapid ranking of compounds according to their binding affinity. In this case, the potential U is defined as... 

Guo et al. [57] used this approach to calculate the binding affinities of different inhibitors of trypsin, shown in Fig. 4.16. They proposed to improve the sampling by adding the following biasing potential ... 

Fig. 4.16. The A dynamics method for alchemical transformations was developed by Guo and Brooks [57] for rapid screening of binding affinities. In this approach the parameter A is a dynamic variable. Techniques like ABF or metadynamics [34] can be used to accelerate this type of calculation. A dynamics was used by Guo [57] to study the binding of benzamidine to trypsin. One simulation is sufficient to gather data on several benzamidine derivatives. Substitutions were made at the para position C5 (H, NH2, CH3 and Cl). The hydrogen atoms are not shown for clarity...

To illustrate these methods, we consider the main biological problems that have motivated their development. The problems that have received the most attention are the receptor-ligand binding problem [12-16] and the calculation of proton binding affinities (pKa shifts) [17-20], The methods described can also be applied to many related problems, such as redox protein behavior, protein-protein association, protein folding, or membrane insertion. 

Free Energy Calculations Methods for Estimating Ligand Binding Affinities... 

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