The power of hard-sphere models: explaining side-chain dihedral angle distributions of Thr and Val.
The energy functions used to predict protein structures typically include both molecular-mechanics and knowledge-based terms. In contrast, our approach is to develop robust physics- and geometry-based methods. Here, we investigate to what extent simple hard-sphere models can be used to predict side-chain conformations. The distributions of the side-chain dihedral angle χ(1) of Val and Thr in proteins of known structure show distinctive features: Val side chains predominantly adopt χ(1) = 180°, whereas Thr side chains typically adopt χ(1) = 60° and 300° (i.e., χ(1) = ±60° or g- and g(+) configurations). Several hypotheses have been proposed to explain these differences, including interresidue steric clashes and hydrogen-bonding interactions. In contrast, we show that the observed side-chain dihedral angle distributions for both Val and Thr can be explained using only local steric interactions in a dipeptide mimetic. Our results emphasize the power of simple physical approaches and their importance for future advances in protein engineering and design.
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
Alice Qinhua
AQ
Zhou
Corey S
CS
O'Hern
Lynne
L
Regan
D030562:Databases, Protein; D004151:Dipeptides / Q000737:chemistry; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D013912:Threonine / Q000737:chemistry*; D014633:Valine / Q000737:chemistry*
D004151:Dipeptides; D013912:Threonine; D014633:Valine