computer modeling in molecular biology.pdf

4 Molecular Dynamics and Free Energy Calculations 85p protons which are part of the backbone whose movement reflects more closely theslower overall tumbling motion of the protein. The small diffusion coefficient of theLys [ protons can be explained by the fact that 3 out of the 4 considered lysines areinvolved in electrostatic interactions with negatively charged protein groups andtherefore do not move freely.Comparison of the data in columns 1 and 2 of Table 4-3 reveals clearly that thediffusion coefficients of the reference proton are virtually identical to those of theslowest water molecules in their first solvent shell. There is one exception however:the lys ( protons diffuse 3 times slower than their most slowly moving first shellwaters.The above results taken together indicate that the motion of water molecules inthe first solvation shell is influenced by the presence of protein groups and possiblyeven coupled to their movements.It is interesting that no difference is detected in the dynamic behavior of watermolecules surrounding polar and hydrophobic groups, a result, which if confirmed,may have an important bearing on our understanding of the hydrophobic effect. Onesees instead that water molecules in contact with groups that are close to or part ofthe protein backbone (fe the amide and p protons) move more slowly than those incontact with flexible sidechains (fe 6 and (protons). This may be due to the fact thatthe movement of water molecules near the polypeptide backbone is hamperedthrough partial shielding from the bulk by nearby sidechains, or through the combinedinfluence of interactions with other backbone atoms. Similar observationsabout the slower movement of water molecules near the backbone than nearsidechain groups were also made in a recent analysis of a 1 ns (1 ns = s)simulation of solvated Bovine Pancreatic Trypsin Inhibitor (BPTI) [26].The slow diffusion coefficient of the ( protons relative to that of their surroundingwater molecules is interesting. It suggests loose coupling between the movementof these water molecules and that of the positively charged protein group. Whetherthis is a general behavior of water surrounding positively charged groups remains tobe seen.A more exhaustive analysis, where averaging is performed on larger ensembles,is clearly needed to verify these observations and to gain further insight.