The mathematics of SELEX against complex targets.

We have developed a computer model for the simulation of simultaneous SELEX against multiple targets. The model assumes equilibrium behavior for the formation of binary ligand:target complexes, and that there is no ligand:ligand or target:target interaction. Target concentrations, ligand concentrations, and affinity distributions of the initial ligand pool for each individual target may be set by the user. We have used this program to gain an understanding of how the presence of multiple targets affects the selection process. In most cases, we find that SELEX is capable of generating different ligands for the different targets in a heterogeneous mixture, regardless of large variations in target concentrations and ligand:target affinities. A low relative partitioning efficiency (the efficiency with which ligands complexed with a target are separated from free ligands) for a target in a mixture gives a greatly reduced rate of selection of high-affinity ligands to that target. The ratio of each high-affinity ligand to its individual target within a pool of ligands selected for binding against a mixture of targets is approximately proportional to the concentration of the target multiplied by the ligand:target partitioning efficiency. Copyright 1998 Academic Press Limited.