A MOLECULAR-DYNAMICS SIMULATION STUDY OF SEGMENT B1 OF PROTEIN-G

The immunoglobulin binding protein, segment B1 of protein G, has been studied experimentally as a paradigm for protein folding, This protein consists of 56 residues, includes both beta sheet and alpha helix and contains neither disulfide bonds nor proline residues, We report an a ll-atom molecular dynamics study of the native manifold of the protein in explicit solvent, A 2-ns simulation starting from the nuclear magn etic resonance (NMR) structure and a 1-ns control simulation starting from the x-ray structure were performed, The difference between averag e structures calculated over the equilibrium portion of trajectories i s smaller than the difference between their starting conformations, Th ese simulation averages are structurally similar to the x-ray structur e and differ in systematic ways from the NMR-determined structure, Par titioning of the fluctuations into fast (<20 ps) and slow (>20 ps) com ponents indicates that the beta sheet displays greater long-time mobil ity than does the alpha helix, Clore and Grronenborn [J. Mol. Biol, 22 3:853-856, 1992] detected two long-residence water molecules by NMR in a solution structure of segment B1 of protein G, Both molecules were found in the fully exposed regions and were proposed to be stabilized by bifurcated hydrogen bonds to the protein backbone, One of these lon g-residence water molecules, found near an exposed loop region, is ide ntified in both of our simulations, and is seen to be involved in the formation of a stable water-mediated hydrogen bond bridge, The second water molecule, located near the middle of the cu helix, is not seen w ith an exceptional residence time in either as a result of the conform ation being closer to the x-ray structure in this region of the protei n. 1997 Wiley-Liss, Inc.