Some slices from the literature
Not too much time this week to dwell in detail on papers, but here are some that I found interesting:
Richard Friesner and his colleagues at Columbia investigate the entropic contribution of arginine side chains by measuring local conformational dynamics by NMR spin relaxation. They compare these results to detailed MD simulations to infer that the aliphatic side chain maintains enough entropy for the charged amino group to fruitfully engage in rigid salt-bridge formation, thus minimizing the entropic penalty.
On the other side of the Atlantic, Angelo Vedani and his colleagues in Basel have derived a QSAR model for psychotropic drugs binding to the glucocorticoid receptor using their programs Yeti and QUASAR. The GR is a nuclear hormone receptor that can modulate a variety of key processes by binding small molecules. The model was validated on 110 compounds representing 4 chemical classes.
An interesting paper on the conformation of a common and important consensus tripeptide motif in a glycoprotein compares measured IR intensities and frequencies using a technique called ion-dip IR spectroscopy to frequencies calculated using high-level ab initio theory (MP2/6-311++G**). The Oxford authors do the comparison for the wild type motif as well as for two mutants and ask a "Why nature selected this specific motif" kind of question by looking at the viability of the resulting conformations. It looks fine, but I am a little skeptical about all those gamma turns that they see, a common artifact of inadequate treatment of solvation in both force field and ab initio approaches.
And again on the medicinal front, a group in Europe does some fragment-based computational design and find a PPAR agonist. Detailed knowledge of protein structure aids in explaining why one bioisostere works and another one does not.