Brownian dynamics simulation of helix‐capping motifs

Helix ‐capping motifs are believed to play an important role in stabilizing α‐helices and defining helix start and stop signals. We performed microsecond scale Brownian dynamics simulations to study ten XAAD sequences, with X = (A,E,I,L,N,Q,S,T,V,Y), to examine their propensity to form helix capping motifs and correlate these results with those obtained from analyzing a structural database of proteins. For the widely studied capping box motif S**D, where the asterisk can be any amino acid residue, the simulations suggested that one of the two hydrogen bonds proposed earlier as a stabilizing factor might not be as important. On the other hand, side‐chain interactions between the capping residue and the third residue downstream on the polypeptide chain might also play a role in stabilizing this motif. These results are consistent with explicit‐solvent molecular dynamics simulations of two capping box motifs found in the proteins BPTI and α‐dendrotoxin. Principal component analysis of the SAAD trajectory showed that the first three principal components, after those corresponding to translational‐rotational motion were removed, accounted for more than half of the conformational fluctuations. The first component separated the conformational space into two parts with the all‐helical conformation and the capping box motif lying largely in one part. The second component, on the other hand, could be used to describe conformational transitions between the all‐helical form and the capping box motif. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 252–259, 2003