Accounting for ligand conformational restriction in estimation of protein-ligand binding affinities
The conformation adopted by a ligand upon binding to a receptor may differ from its lowest-energy conformation in solution. In addition, the bound ligand is more conformationally restricted, which is associated with an entropic cost. Accounting for these effects can improve the accuracy of affinity calculations. Below: the enzyme scytalone dehyradratase (left) and inhibitors (right). The conformation in red is the bound state; blue, the most favorable in solution; turquoise, other conformations observed in solution.
Molecular dynamics simulations of the G protein βγ heterodimer
G proteins are involved in signal transduction and interact with a wide range of binding partners. NMR and molecular dynamics simulations show large mobility of a tryptophan near the binding surface of the G protein βγ heterodimer and suggest that there is conformational flexibility that could be exploited during molecular recognition. Below: Trp residues in Gβ and trajectories for ϕ, ψ, χ1, and χ2 dihedral angles for GβW99 and GβW332 from molecular dynamics simulations.
Mixed quantum-mechanics/molecular mechanics calculations to examine spectral tuning in opsins
Our calculations suggest that shifts in the absorbance spectrum of retinal are primarily due to electrostatic rather than steric or geometric effects, and that these are due to the entire opsin protein including residues far away from the chromophore.
