Interaction of explicit solvent with hydrophobic/philic/charged residues of a protein: residue character vs. conformational context.

Molecular dynamics simulations of model solutes in explicit molecular water have recently elicited novel aspects of the strong nonpair additivity of the potential of mean force (PMF) and related solvent-induced forces (SIFs) and hydration. Here we present the results of the same type of work on SIFs acting on bovine pancreatic trypsin inhibitor (BPTI) at single residue/sidechain resolution. In this system, nonpair additivity and the consequent dependence of SIFs on the protein conformational context are sufficiently strong to overturn SIFs on some individual residues, relative to expectations based on their individual characters. This finding calls for a revisitation and offers a richer and diversified understanding of the role of hydrophobic/philic/charged groups in establishing the exquisite specificity of biomolecular folding and functional conformation. Its relevance is appreciated by noting that the work of a typical SIF acting on one residue, when displaced across a distance of 1 A, is the equivalent of up to a few kcal/mol, which is the range of the stability/function free energy of a protein.

[Merkel cell carcinoma of the skin. Two clinical cases]. / Carcinoma a cellule di Merkel della cute. Considerazioni su due casi clinici.

In this study are described two clinical cases of Merkel cell tumor treated in the first half of 1991. The MCC is a rare primary skin tumor with an aggressive biologic nature. The elective therapy of primary sites is surgical management with lymphadenectomy although this kind of treatment is debated. Local recurrence high incidence requires a frequent and careful follow-up with possibility of second surgical treatment in the cases without metastasis and a radiochemotherapy in the patients affected by systemic recurrences.

[Hydatid choleperitoneum: a rare complication of hepatic hydatid disease]. / Idatidocoleperitoneo: rara complicanza della idatidosi epatica.

The authors report their experience relative to hydatid choleperitoneum which is a rare complication of hydatid hepatic disease (one case of 236 operated). They underline how such pathology constitutes a clinic and anatomopathological case, well characterized and different from those offered by other complications of this hepatic disease. They draw attention moreover on how preoperative diagnosis is often difficult and consequently how the surgical therapeutic technique requires a very careful examination of anatomic relations of the lesion and recognize, as a chiefly foundation, a radical treatment of hepatic disease and whenever possible, the removal of the pseudomembrane of encystment.

The hydration shell of myoglobin.

The space in the unit cell of a metmyoglobin crystal not occupied by myoglobin atoms was filled with water using Monte Carlo calculations. Independent calculations with different amounts of water have been performed. Structure factors were calculated using the water coordinates thus obtained and the known coordinates of the myoglobin atoms. A comparison with experimental structure factors showed that both the low and the high resolution regime could be well reproduced with 814 Monte Carlo water molecules per unit cell with a B-value of 50 A2. The Monte Carlo water molecules yield a smaller standard R-value (0.166) than using a homogeneous electron density for the simulation of the crystal water (R = 0.212). A reciprocal space refinement of the water and the protein coordinates has been performed. Monte Carlo calculations can be used to obtain information for crystallographically invisible parts of the unit cell and yield better coordinates for the visible part in the refinement.

Molecular dynamics simulation in vacuo and in solution of cyclolinopeptide A: a conformational study.

The conformation of cyclolinopeptide A [c-(Pro-Pro-Phe-Phe-Leu-Ile-Ile-Leu-Val)], a naturally occurring peptide with remarkable cytoprotective activity, has been investigated by means of molecular dynamics simulations in various molecular environments. Structural and dynamical properties have been analyzed and compared with those experimentally determined. A detailed analysis of hydrogen bonds is reported.

Computer simulations of complex chemical systems.

In this paper, after a brief description on our approach to simulations of chemical systems, some of the results obtained are discussed. Four examples are reported: 1) liquid water simulation which takes in account a four-body potential; 2) hydration networks in a crystal; 3) water and ion structures in DNA; 4) proton tunneling in DNA base pairs. We include also a short description of a parallel system we have assembled.

Networks of water molecules in a proflavine deoxydinucleoside phosphate complex.

Using previously reported ab-initio atom-atom potentials for the interactions of a water molecule with phosphates, sugars and bases and newly computed ab-initio atom-atom potentials for the interaction between a proflavine ion and water, we have analyzed with the Monte-Carlo Metropolis method networks of water molecules hydrating a 2:2 complex of proflavine and deoxycytidylyl-3',5'-guanosine, recently studied with X-ray crystallography. From our simulations we have i) verified the quality of our atom-atom potentials by obtaining patterns of oxygen atoms in very good agreement with the X-ray patterns for the minor groove and in reasonable agreement in the major groove, ii) predicted the water's hydrogen atoms positions and iii) preliminarily predicted the number of water molecules not reported in the X-ray study but present in the major groove. The above data, even if preliminary, and the analyses on the energetics of the water-water, water-proflavine and water-dCpG interactions indicate that very detailed accounts on the water filaments in the above crystal can be obtained optimally by merging computer and X-ray experiments.

Simulations of the solvent structure for macromolecules: solvation model for B-DNA and Na+-B-DNA double helix at 300 degrees K.

The structure of water and the energy of its interaction with a fragment of B-DNA composed of 12 based-pairs and with the corresponding sugar and phosphate units and Na+ ions (at each phosphate group) are analyzed using Monte Carlo stimulations. The sample of water molecules, at the stimulated temperature of 300 degrees K, is composed of 447 water molecules. The results are discussed either in terms of a statistical analysis over the two million stimulated conformations (after equilibration) or with reference to an "average configuration." A comparison is made with a simulation previously presented for the same system but without counterions. Isotherms at different relative humidity, hydration, and tentative reactivity scales for different sites; the hydration number at each site; and the structure of interphosphate and intraphosphate hydrogen bonded filaments of water are reported and discussed. The stabilization of the B-conformation induced by the solvent with counterion ("ion-induced compression effect") is analyzed on the basis of the above findings. The analysis presented is very detailed to allow refined interpretations of spectroscopic (infrared, Rahman, and nmr) and scattering (x-rays and neutron beams) data on DNA in solution.