Buried water molecules

Clearly, the value of -12 kcal/mol for the threshold energy is not accidental. Buried water molecules are in equilibrium with water nioh cules in the... 

Table 2 shows the results of our preliminary calculations of the pKa of the Cys403 residue, for several different models of the enzyme, based on two structures available from the PDB. In the case of the YPT structure, a crystal water molecule is close to Cys403 and was included in some of the calculations as part of the protein (i.e. it was treated with the same internal dielectric as that of the protein). Simulations denoted as -I-H2O in Table 2, include a crystallographically resolved, buried water molecule, situated 3.2lA from... 

Bo is the measurement frequency. Rapid exchange between the different fractions is assumed the bulk, water at the protein surface (s) and interior water molecules, buried in the protein and responsible for dispersion (i). In fact, protons from the protein surface exchanging with water lead to dispersion as well and should fall into this category Bulk and s are relevant to extreme narrowing conditions and cannot be separated unless additional data or estimations are available (for instance, an estimation of fg from some knowledge of the protein surface). As far as quadrupolar nuclei are concerned (i.e., and O), dispersion of Rj is relevant of Eqs. (62) and (63) (this evolves according to a Lorentzian function as in Fig. 9) and yield information about the number of water molecules inside the protein and about the protein dynamics (sensed by the buried water molecules). Two important points must be noted about Eqs. (62) and (63). First, the effective correlation time Tc is composed of the protein rotational correlation time and of the residence time iw at the hydration site so that... 

Not all structure-based design experiments are successful. Attempts to displace the arginine residue that caps the SI pocket of HFC by forming a salt link with carboxylate or hydroxyl moiety were unsuccessful [42]. However, these failed attempts offer some redeeming features in the refinement of parameters that can be used to evaluate the energetic potentials for displacing buried water molecules as well as the inherent desolvation energies for polar compounds. 

The buried water molecule noticed in the crystal structure of this and many other inhibitor complexes is tetrahedrally coordinated to both the inhibitor and the flaps of the enzyme. Randad et al. (1993) have used molecular modelling based on the crystal structures to incorporate the water oxygen atom as the carbonyl oxygen of novel, cyclic ureas (67). They reasoned that displacement of the water should be energetically favourable... 

The only significant differences between the two redox forms of cytochrome c involve a buried water molecule, which is hydrogen bonded to Asn-52, Tyr-67 and Thr-78. The water molecule is further from the heme by 1.0 A and the heme is deeper in the crevice by 0.15 A in the reduced protein, giving a less polar environment. 

Bound solvent molecules are an integral part of the structures of their proteins. This is seen in the extensive hydrogen bond networks that they form and that bridge protein atoms. Such cross-linking is observed internally as well as externally many globular proteins contain a number of buried water molecules. The water molecule is unique because it has both double-donor and double-acceptor capability. 

Internal water is an integral part of a protein structure. Even globular proteins of small size are observed to contain buried water molecules. Examples are pancreatic trypsin inhibitor, with 58 amino acid residues and 4 interior water molecules, lysozyme with 129 residues and 4 waters, and larger proteins like ac-tinidin with 218 residues which may contain 10 to 20 molecules of internal water (Fig. 19.13). These water molecules can be buried deep inside the globular proteins or located in cavities near the surface. In some cases, therefore, the distinction in-ternal/external water can be ambiguous. 

Thrombin binds sodium better than potassium. The cation is bound by backbone carbonyl groups of Arg22 la and Lys224 and by four buried water molecules. One water molecule connects the sodium ion to OD2 of Asp819 this accounts for the primary specificity of the enzyme. When sodium is released, Asp819 reorients and this perturbation extends to the catalytic site. 

Although DMP-323 replaces one buried water molecule, several others are observed in... 

Our simulations shows that both CTWAT and CTMONO have lower RMS deviations compared to the CT system, indicating that they have a closer resemblance to the starting crystal structure (Table l).If we assume that CTMONO represents an aqueous simulation, this is in contrast to our earlier work on BPTI where we found that the RMS deviation was on average higher for the BPTI in water system. This difference is more obvious in the RMS deviation of the backbone atoms only. We further found the change in the placement of the 50 "essential" water molecules from CT to CTWAT have resulted in significant difference in RMS deviations. It has been reported that the correct placement of buried water molecules is necessary to obtain locally correct structure. ... 

In hPL the H-bond between Asp-177(081) and His-264(N81) is unique in that it is of an anti type (Fig. 5D). Moreover, the syn pair of electrons on 081 is free. The stability of the Asp-177 side chain is achieved by a a three-centered H-bond involving the anti pair of electrons on 082, the amide hydrogen of Thr-204, and a buried water molecule. Again, the syn pair of electrons on 082 is free. 

The polar cavity of Asp-102 also includes two buried water molecules, as well as backbone amides of Ala-56 and His-57. In about 200 SP, all but three have this Ser-214 residue. It is solvent inaccessible, and its OG forms a hydrogen bond to Asp-102. In an extensive experimental study by McGrath et al.(1992), Ser-214 has been mutated to Ala, Glu and Lys in rat anionic trypsin and both kinetics and crystallography were employed to study the... 

Figure 3. A schematic diagram showing the intermolecular hydrogen bonding network between influenza virus sialidase, including three buried water molecules, and bound NeuSAc.

The X-ray crystal-structure determination revealed a lack of any direct, helix-helix interaction between the a- and P-polypeptides within the hydrophobic core, as had been expected on the basis of earlier models [see Fig. 4 (B) and (C) above]. The association of the fMet-1 residue at the N-terminal of each a-polypeptide to a B800 BChl-a molecule prevents direct interaction between radially paired a-and P-helices. Interactions between the membrane-core helices are mediated only via pigment molecules or buried water molecules. The only polypeptide interaction occurs at the N- and C-terminal tails. In the C-terminal tail the large aromatic residues (a-Trp 40, a-Tyr 44, a-Trp 45 and P-Trp 39) contribute to binding between polypeptides via hydrogen bonds and hydrophobic interactions [see Fig. 5 (C)]. 

Thinking about the hydration of protein complexes is simplified by dividing water molecules into four classes bulk water molecules that are not directly in contact with the biomolecules, surface water hydrogen bonded to the protein or ligand, surface water associated with apolar biomolecular groups, and buried water molecules that have no direct connection to the bulk solvent. 

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