Jbo. Mitchell et al., A COMPARISON OF 3 THEORETICAL APPROACHES TO THE STUDY OF SIDE-CHAIN INTERACTIONS IN PROTEINS, Journal of the Chemical Society. Faraday transactions, 89(15), 1993, pp. 2619-2630
Citations number
46
Categorie Soggetti
Chemistry Physical","Physics, Atomic, Molecular & Chemical
The continuing increase in the number of high-quality protein crystal
structures means that a considerable amount of data is now available t
o those studying the interactions of side-chain atoms. These experimen
tal data can be used as a benchmark for theoretical studies of the spa
tial distributions of side-chain-atom and side-chain-side-chain intera
ctions. We use the program suite SIRIUS to calculate experimental side
-chain-atom distributions, complementing the existing side-chain-side-
chain distributions, for each of four systems: phenylalanine-carboxyla
te, phenylalanine-aromatic, arginine-carboxylate, and arginine-aromati
c. Three theoretical methods are tested: first the drug design program
GRID, which is suited to calculating side-chain-atom distributions, s
econdly the distributed multipole analysis (DMA) electrostatic approac
h, and thirdly the empirical potential CHARMm. We look at the predicti
ons of each method for the four systems, and compare theory with exper
iment. Our results show that the strongly hydrogen-bonded arginine-car
boxylate interaction is relatively easy to model, but that proper desc
ription of aromatic systems requires an explicit representation of the
pi-electrons, as modelled by the atomic quadrupoles in DMA. For argin
ine-aromatic, we have to consider the effect of competing interactions
before we can successfully reconcile experiment with theory.