Jun 13, 2015

Strong Ligand-Protein Interactions Derived from Diffuse Ligand Interactions with Loose Binding Sites

BioMed Research International
Lorraine Marsh

Abstract

Many systems in biology rely on binding of ligands to target proteins in a single high-affinity conformation with a favorable ΔG. Alternatively, interactions of ligands with protein regions that allow diffuse binding, distributed over multiple sites and conformations, can exhibit favorable ΔG because of their higher entropy. Diffuse binding may be biologically important for multidrug transporters and carrier proteins. A fine-grained computational method for numerical integration of total binding ΔG arising from diffuse regional interaction of a ligand in multiple conformations using a Markov Chain Monte Carlo (MCMC) approach is presented. This method yields a metric that quantifies the influence on overall ligand affinity of ligand binding to multiple, distinct sites within a protein binding region. This metric is essentially a measure of dispersion in equilibrium ligand binding and depends on both the number of potential sites of interaction and the distribution of their individual predicted affinities. Analysis of test cases indicates that, for some ligand/protein pairs involving transporters and carrier proteins, diffuse binding contributes greatly to total affinity, whereas in other cases the influence is modest. This appro...Continue Reading

Mentioned in this Paper

Protein Binding
Ligand Binding
Tertiary Protein Structure
Plasma Protein Binding Capacity
Site
Ligand Binding Domain
Protein Conformation
Binding (Molecular Function)
Membrane Transport Proteins
Analysis

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