Bioisosteric replacements and scaffold hopping play an important role in modern drug discovery and design, as they enable the change of either a core scaffold or substitutes in a drug structure, thereby facilitating optimization of pharmacokinetic properties and patenting, while the drug retains its activity. A new knowledge-based method was developed to obtain bioisosteric or scaffold replacem...

The impact of an amino acid replacement on the organism's fitness can vary from lethal to selectively neutral and even, in rare cases, beneficial. Substantial data are available on either pathogenic or acceptable replacements. However, the whole distribution of coefficients of selection against individual replacements is not known for any organism. To ascertain this distribution for human prote...

Reassortments and point mutations are two major contributors to diversity of Influenza A virus; however, the link between these two processes is unclear. It has been suggested that reassortments provoke a temporary increase in the rate of amino acid changes as the viral proteins adapt to new genetic environment, but this phenomenon has not been studied systematically. Here, we use a phylogeneti...

OBJECTIVES To examine how comorbid diseases (cardiovascular diseases, hypertension, diabetes, cancer, pulmonary diseases, depression, psychotic disorders and neurodegenerative diseases) affect survival of hip and knee replacements. METHODS Data for this register-based study were collected by combining data from five nationwide health registers. 43 747 primary total hip and 53 007 primary tota...

Introduction: The demand for joint replacements in young patients is increasing, and therefore there is a need to increase the lifetime of the prostheses. To fulfil this requirement, new replacements’ designs and materials are being introduced. One of the design parameters that may affect wear of total knee replacements, and hence the predicted lifetime of such prostheses, is the insert conform...

Evolution of sequences mostly involves independent changes at different sites. However, substitutions at neighboring sites may co-occur as multinucleotide replacement events (MNRs). Here, we compare noncoding sequences of several species of primates, and of three species of Drosophila fruit flies, in a phylogenetic analysis of the replacements that occurred between species at nearby nucleotide ...