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Mutations are the source of evolutionary variation. The interactions of multiple mutations can have important effects on fitness and evolutionary trajectories. We have recently described the distribution of fitness effects of all single mutations for a nin ...
Human cytomegalovirus (HCMV) exhibits surprisingly high genomic diversity during natural infection although little is known about the limits or patterns of HCMV diversity among humans. To address this deficiency, we analyzed genomic diversity among congeni ...
This work examines the conformational ensemble involved in beta-hairpin folding by means of advanced molecular dynamics simulations and dimensionality reduction. A fully atomistic description of the protein and the surrounding solvent molecules is used, an ...
Enzymes have evolved during millions of years to become efficient catalysts for specific biochemical reactions within a specific range of working conditions in the cellular environment. The activity of an enzyme is directly related to its folded structure ...
We have targeted the Mycobacterium tuberculosis decaprenylphosphoryl-beta-D-ribose oxidase (Mt-DprE1) for potential chemotherapeutic intervention of tuberculosis. A multicopy suppression strategy that overexpressed Mt-DprEl in M. bovis BCG was used to prof ...
The physical chemical principles underlying,enzymatic thermostability are keys to understand the way evolution has shaped proteins,to adapt to a broad range of temperatures. Understanding the molecular determinants at the basis of protein thermostability i ...
Sequencing projects have identified large numbers of rare stop-gain and frameshift variants in the human genome. As most of these are observed in the heterozygous state, they test a gene's tolerance to haploinsufficiency and dominant loss of function. We a ...
DNA molecule is the fundamental component of every living organism, since it encodes the hereditary information. Although the genetic code of almost 200 species has been sequenced, the direct connection between gene sequence, DNA structure and biological f ...
Adaptation lies at the heart of Darwinian evolution. Accordingly, numerous studies have tried to provide a formal framework for the description of the adaptive process. Of these, two complementary modeling approaches have emerged: While so-called adaptive- ...
Background and Purpose: Transgenic mice over-expressing Notch2 in the uvea exhibit a hyperplastic ciliary body leading to increased IOP and glaucoma. The aim of this study was to investigate the possible presence of NOTCH2 variants in patients with primary ...