Computer modeling of ligand

Kent, R. S., De Lean, A., and Lefkowitz, R. J. (1980). A quantitative analysis of beta-adrenergic receptor interactions Resolution of high and low affinity states of the receptor by computer modeling of ligand binding data. Mol. Pharmacol. 17, 14-23. 

III. Structure-based computational models of ligand-protein binding dynamics and molecular docking... 

If structural information of the protein target is available, e.g., a crystal structure, in silico screening of huge virtual compound libraries can be conducted by the use of docking simulations. Based on identified primary hits, structural variations of the ligand can be evaluated by computational modeling of the ligand-protein complex. 

As idealized computational models of metal hypovalency, let us therefore consider the early second-series transition-metal hydrides YH3, ZrH4, and NbfL (avoiding both the complications of lone-pair-bearing ligands and those associated with the lanthanide series). Figure 4.54 shows optimized structures of these species, and Table 4.33 summarizes the bonding (omh) and nonbonding (nM ) orbitals and occupancies at the metal center. 

Lopez-Rodriguez, M.L., Morcillo, M.J., Fernandez, E., Rosado, M.L., Pardo, L. and Schaper, K.-f. (2001) Synthesis and structure-activity relationships of a new model of arylpiperazines. 6. Study of the 5-HTiA/ai-adrenergic receptor affinity by classical Hansch analysis, artificial neural networks, and computational simulation of ligand recognition. Journal of Medicinal Chemistry, 44, 198-207. 

Verkhivker GM (2004) Computational analysis of ligand binding dynamics at the intermolecular hot spots with the aid of simulated tempering and binding free energy calculations, Mol J Graph Model, 22(5) 335-348... 

Even more impressive is the development of appropriate analytics. Modern NMR technology reveals such perfect complementarity as in the case of glycopep-tides at levels of atomic resolution, providing virtual threedimensional models of ligand protein interaction. Bacterial resistance and means to cope with it, can be discussed by studying models of chiral interaction in the computer. 

As with many computational models of catalysis, we need a key step in the mechanism to model. Since chain growth occurs with the olefin trans to the coordinated oxygen, workers at Shell have modeled the cis/trans ratio in order to determine how to modify the ligand to force trans coordination (Fig. 12). 

Many attempts have been made to rehne the ligand held treatment of substitution kinetics, and computer modeling of solvent exchange in particular (Section 8.7) has lately become almost a discipline in its own right, but there is as yet no panacea. The basic LFAE concept, however, does provide readily comprehensible qualitative... 

Oda, A., Tsuchida, K., Takakura, T, Yamaotsu, N., and Hirono, S. (2005) Comparison of consensus scoring strategies for evaluating computational models of protein-ligand complexes. Journal of Chemical Information and Modeling, 46, 380-391. 

---