@article{10.1371/journal.pcbi.1003274, doi = {10.1371/journal.pcbi.1003274}, author = {Ruiz-Herrero, Teresa AND Estrada, Javier AND Guantes, Raúl AND Miguez, David G.}, journal = {PLOS Computational Biology}, publisher = {Public Library of Science}, title = {A Tunable Coarse-Grained Model for Ligand-Receptor Interaction}, year = {2013}, month = {11}, volume = {9}, url = {https://doi.org/10.1371/journal.pcbi.1003274}, pages = {1-8}, abstract = {Cell-surface receptors are the most common target for therapeutic drugs. The design and optimization of next generation synthetic drugs require a detailed understanding of the interaction with their corresponding receptors. Mathematical approximations to study ligand-receptor systems based on reaction kinetics strongly simplify the spatial constraints of the interaction, while full atomistic ligand-receptor models do not allow for a statistical many-particle analysis, due to their high computational requirements. Here we present a generic coarse-grained model for ligand-receptor systems that accounts for the essential spatial characteristics of the interaction, while allowing statistical analysis. The model captures the main features of ligand-receptor kinetics, such as diffusion dependence of affinity and dissociation rates. Our model is used to characterize chimeric compounds, designed to take advantage of the receptor over-expression phenotype of certain diseases to selectively target unhealthy cells. Molecular dynamics simulations of chimeric ligands are used to study how selectivity can be optimized based on receptor abundance, ligand-receptor affinity and length of the linker between both ligand subunits. Overall, this coarse-grained model is a useful approximation in the study of systems with complex ligand-receptor interactions or spatial constraints.}, number = {11}, }