PHEPS (pH-dependent Protein Electrostatics Server) is a web service for fast prediction and experiment planning support, as well as for correlation and analysis of experimentally obtained results, reflecting charge-dependent phenomena in globular proteins. Its implementation is based on long-term experience (PHEI package) and the need to explain measured physicochemical characteristics at the level of protein atomic structure. The approach is semi-empirical and based on a mean field scheme for description and evaluation of global and local pH-dependent electrostatic properties: protein proton binding; ionic sites proton population; free energy electrostatic term; ionic groups proton affinities (pKa,i) and their Coulomb interaction with whole charge multipole; electrostatic potential of whole molecule at fixed pH and pH-dependent local electrostatic potentials at user-defined set of points. The speed of calculation is based on fast determination of distance-dependent pair charge-charge interactions as empirical three exponential function that covers charge–charge, charge–dipole and dipole–dipole contributions. After atomic coordinates input, all standard parameters are used as defaults to facilitate non-experienced users. Special attention was given to interactive addition of non-polypeptide charges, extra ionizable groups with intrinsic pKas or fixed ions. The output information is given as plain-text, readable by ‘RasMol’, ‘Origin’ and the like. The PHEPS server is accessible at .

PHEMTO (protein pH-dependent electric moment tools) is released in response to the high demand in protein science community for evaluation of electrostatic characteristics in relations to molecular recognition. PHEMTO will serve protein scientists with new advanced features for analysis of protein molecular interactions: Electric/dipole moments, their pH-dependence and in silico charge mutagenesis effects on these properties as well as alternative algorithms for electric/dipole moment computation—Singular value decomposition of electrostatic potential (EP) to account for reaction field. The implementation is based on long-term experience—PHEI mean field electrostatics and PHEPS server for evaluation of global and local pH-dependent properties. However, PHEMTO is not just an update of our PHEPS server. Besides standard electrostatics, we offer new, advanced and useful features for analysis of protein molecular interactions. In addition our algorithms are very fast. Special emphasis is given to the interface—intuitive and user-friendly. The input is comprised of the atomic coordinate file in Protein Data Bank format. The advanced user is provided with a special input section for addition of non-polypeptide charges. The output covers actually full electrostatic characteristics but special emphasis is given to electric/dipole moments and their interactive visualization. PHEMTO server can be accessed at http://phemto.orgchm.bas.bg/.

Classical complement pathway is an important innate immune mechanism, which is usually triggered by binding of C1q to immunoglobulins, pentraxins and other target molecules. Although the activation of the classical pathway is crucial in the host defence, its undesirable and uncontrolled activation can lead to tissue damage. Thus, understanding the molecular basis of complement activation and its inhibition are of great biomedical importance. Recently, we proposed a mechanism for target recognition and classical pathway activation by C1q, which is likely governed by calcium-controlled reorientation of macromolecular electric moment vectors. Here we sought to define the mechanism of C1q inhibition by low molecular weight disulphate compounds that bind to the globular (gC1q) domain, using experimental, computational docking and theoretical modelling approaches. Our experimental results demonstrate that betulin disulphate (B2S) and 9,9-bis(4'-hydroxyphenyl)fluorene disulphate (F2S) inhibit the interaction of C1q and its recombinant globular modules with target molecules IgG1, C-reactive protein (CRP) and long pentraxin 3 (PTX3). In most C1q-inhibitor docked complexes, there is a reduction of electric moment scalar values and similarly altered direction of electric/dipole moment vectors. This could explain the inhibitory effect by impaired electrostatic steering, lacking optimal target recognition and formation of functional complex. In the presence of the inhibitor, the tilt of gC1q domains is likely to be blocked by the altered direction of the electric moment vector. Thus, the transition from the inactive (closed) towards the active (open) conformation of C1q (i.e. the complement activation signal transmission) will be impaired and the cascade initiation disrupted. These results could serve as a starting point for the exploration of a new form of 'electric moment inhibitors/effectors'.

Quantum.Ligand.Dock (protein–ligand docking with graphic processing unit (GPU) quantum entanglement refinement on a GPU system) is an original modern method for in silico prediction of protein–ligand interactions via high-performance docking code. The main flavour of our approach is a combination of fast search with a special account for overlooked physical interactions. On the one hand, we take care of self-consistency and proton equilibria mutual effects of docking partners. On the other hand, Quantum.Ligand.Dock is the the only docking server offering such a subtle supplement to protein docking algorithms as quantum entanglement contributions. The motivation for development and proposition of the method to the community hinges upon two arguments—the fundamental importance of quantum entanglement contribution in molecular interaction and the realistic possibility to implement it by the availability of supercomputing power. The implementation of sophisticated quantum methods is made possible by parallelization at several bottlenecks on a GPU supercomputer. The high-performance implementation will be of use for large-scale virtual screening projects, structural bioinformatics, systems biology and fundamental research in understanding protein–ligand recognition. The design of the interface is focused on feasibility and ease of use. Protein and ligand molecule structures are supposed to be submitted as atomic coordinate files in PDB format. A customization section is offered for addition of user-specified charges, extra ionogenic groups with intrinsic pKa values or fixed ions. Final predicted complexes are ranked according to obtained scores and provided in PDB format as well as interactive visualization in a molecular viewer. Quantum.Ligand.Dock server can be accessed at http://87.116.85.141/LigandDock.html.

We attempted to attain atomic-scale insights into the mechanism of the heat-induced phase transition of two thermoresponsive polymers containing amide groups, poly(N-isopropylacrylamide) (PNIPAM) and poly(2-isopropyl-2-oxazoline) (PIPOZ), and we succeeded in reproducing the existence of lower critical solution temperature (LCST). The simulation data are in accord with experimental findings. We found out that the entropy has an important contribution to the thermodynamics of the phase separation transition. Moreover, after decomposing further the entropy change to contributions from the solutes and from the solvent, it appeared out that the entropy of the solvent has the decisive share for the lowering of the free energy of the system when increasing the temperature above the LCST. Our conclusion is that the thermoresponsive behavior is driven by the entropy of the solvent. The water molecules structured around the functional groups of the polymer that are exposed to contact with the solvent in the extended conformation lower the enthalpy of the system, but at certain temperature the extended conformation of the polymer collapses as a result of dominating entropy gain from “released” water molecules. We stress also on the importance of using more than one reference molecule in the simulation box at the setup of the simulation.