Introduction of drugs puts an evolutionary pressure on viruses and makes the viral proteins evolve. On the other hand, the change in the protein structure should be compatible with the protein function. The degree of the protein sequence conservativity is thus a measure of the structural importance of a particular region on the protein surface. Certain binding sites are evolving and mutate often, certain are not. Finding the most conservative fractions of a target protein sequence can help identify important and druggable binding sites for inhibitors search, find drugs with the least potential for drug resistance development.

Below we provide an analysis of H5N1 neuromidase protein surface next to the tamiflu binding region. The Figure shows the level of protein structure conservation, red portions corresponds to the most conservative residues. A small yellow patch of the pocket has evolved since 1990 and gave way to develop tamiflu resistance.

The analysis shows that in spite of a lot of pressure from the drug application, the virus was not able to change the red part of the pocket. Future drugs should target the binding sites with the least mutable residues.

Free Energy perturbation molecular dynamics demonstration. The calculation lets the molecule escape from the binding site and give the free energy difference, directly related to the binding affinity

ss DNA Molecular dynamics trajectory using the latest Quantum force field helps to find a perfectly stable conformation of the biomolecule in solution. The outcome of the simulation is very reasonable, given the fact that ss DNA (such as telomers) tend indeed to form such loops (see the Figure on the right). The Figure shows the structure of a DNA quadruplex formed by telomere repeats. The conformation of the DNA backbone diverges significantly from the typical helical structure

Quantum LogP module (part of q-Mol package) has been reviewed by R. Mannhold et al. (vcclab.org) in "Calculation of Molecular Lipophilicity: State-of-the-Art and Comparison of Log P Methods on More Than 96,000 Compounds". From the manuscript:

"Quantum LogP, developed by Quantum Pharmaceuticals, uses another quantum-chemical model to calculate the solvation energy. Like in COSMO-RS, the authors do not explicitly consider water molecules but use a continuum solvation model. However, while the COSMO-RS model simplifies solvation to interaction of molecular surfaces, the new vector-field model of polar liquids accounts for short-range (H-bond formation) and long-range dipole–dipole interactions of target and solute molecules Quantum LogP calculated log P for over 900 molecules with an RMSE of 0.7 and R2 of 0.94".

Molecular modelling software of Quantum Pharmaceuticals is used to dock small molecule to active site of target protein. The molecular docking on flexible protein is explored. The Quantum docking software is available for free use at LeadFinding.com, the online hit-to-lead optimization service to filter and profile chemical compounds in chemical database of ChemDiv - organic chemistry supplier.