Here we extend the ability to predict hydrodynamic coefficients and other solution properties of rigid macromolecular structures from atomic-level structures, implemented in the computer program HYDROPRO, to models with lower, residue-level resolution. Whereas in the former case there is one bead per nonhydrogen atom, the latter contains one bead per amino acid (or nucleotide) residue, thus allowing calculations when atomic resolution is not available or coarse-grained models are preferred. We parameterized the effective hydrodynamic radius of the elements in the atomic- and residue-level models using a very large set of experimental data for translational and rotational coefficients (intrinsic viscosity and radius of gyration) for >50 proteins. We also extended the calculations to very large proteins and macromolecular complexes, such as the whole 70S ribosome. We show that with proper parameterization, the two levels of resolution yield similar and rather good agreement with experimental data. The new version of HYDROPRO, in addition to considering various computational and modeling schemes, is far more efficient computationally and can be handled with the use of a graphical interface.

A Monte Carlo simulation, coupled with beadmodel hydrodynamic calculation, has been employed to predict hydrodynamic coefficients and other solution properties, of wormlike macromolecules, covering the full range of the wormlike model, from short cylinders to very long, fully flexible chains, eventually including excluded-volume effects. The results have been implemented in a computational tool, Multi-HYDFIT, which performs the determination of the structural parameters from a set of experimental data of various properties for multiple samples with varying molecular weight. An analysis of experimental data of double-stranded DNA demonstrates that the Multi-HYDFIT treatment, with our simulation results, predicts the various solution properties of DNA in an extremely wide range of sizes, from 8 to 200 000 base pairs, yielding values of the parameters that agree with those of the double helix. The scheme is also applied to other synthetic and biological macromolecules, like the very stiff, triple-helical schizophyllan polysaccharide or the very flexible poly(isobutylene) polymer, the latter covering again an extremely wide range that includes quite short oligomers.

The HIV-1 gp41 envelope glycoprotein is responsible for the membrane fusion between the virus and the target cell. According to recent models, the N-terminal coiled-coil (NHR) region of gp41 is involved in forming the interfaces between neighboring helices in the six-helix bundle, as well as in membrane binding and perturbation. In order to get new insights into the viral membrane fusion mechanism, two peptides, pFP15 and pFP23, pertaining to the first part of the gp41 NHR domain were studied regarding their structure and their ability to induce membrane leakage, aggregation, and fusion, as well as their affinity toward specific phospholipids by a variety of spectroscopic methods. Our results demonstrate that the first part of the NHR domain interacts with negatively charged phospholipid-containing model membranes, modifies the phase behavior of membrane phospholipids, and induces leakage and aggregation of liposomes, suggesting that it could be involved directly in the merging of the viral and target cell membranes working synergistically with other membrane-active regions of the gp41 glycoprotein to boost the fusion process. On the other hand, we suggest that this region of the NHR domain could be involved in the first steps of the destabilization of the HIV-1 gp41 six-helix bundle after its interaction with negatively charged phospholipid headgroups.

The calculation of the intrinsic viscosity by means of classical treatments of bead models, typically composed of a number of identical beads, presents some problems when applied to models where the beads are unequal and their number is not very large. A correction to this problem was proposed 10 years ago (García de la Torre and Carrasco in Eur Biophys J 27:549-557, 1998). This so-called volume correction, which consisted of adding a term proportional to the volume of the model, was proved to be rigorous in physico-mathematical terms, and produced improved results in some circumstances, but not always. Recently, the volume correction is being reconsidered so that with some deduced or empirical modifications, it can allow for safer predictions of the intrinsic viscosity. This paper contributes a discussion and further improvements of that correction for the intrinsic viscosity.

The possibility of validating structures of intrinsically disordered proteins against solution properties is a goal that would be most helpful in the understanding of their function. We have devised a scheme for the prediction of solution properties of partially disordered proteins that comprise one or more ordered domains, along with flexible tails or linkers. A very simple, coarse-grained, residue-level model, which is easily parametrized using available structural information, along with previously developed tools for the simulation of solution conformation and dynamics, allows the prediction of properties like sedimentation coefficients, relaxation times, and X-ray or neutron scattering. This is demonstrated for a variety of partially disordered proteins, for which well-characterized solution properties are very accurately evaluated, with predictions falling in most cases within experimental errors.